Navigation & Localization, 2024:8
Time cells emerge early in learning and encode stimulus modality past task requirements
2024-12-10, bioRxiv (10.1101/2024.07.28.605458) (online) (PDF)Upinder S Bhalla, Soumya Bhattacharjee, and Hrishikesh Nambisan (?)
Hippocampal neurons represent multiple dimensions of stimulus and behavioural context, including time. It is unclear how soon time-encoding cells emerge during learning, and if they additionally encode context in a manner specific to behavioural paradigm. We investigated simultaneous time and context encoding using 2-photon calcium imaging of mouse hippocampus during a trace eyeblink conditioning (TEC) task with sound and light stimuli. We find that the fraction of time cells is independent of learning and of stimulus modality. Only 13% of cells retain time-encoding on successive days, but persisters remain active within their original stimulus and post-stimulus epochs. Finally, we show that 60% of modality-specific time-encoding cells are active after the stimulus period, but modality-agnostic time cells are rare post-stimulus. Thus, compared to other paradigms, time cells in TEC have distinct learning and turnover properties, and exhibit sustained coding of stimulus modality and time which may subserve associations with subsequent events.
Added on Wednesday, December 11, 2024. Currently included in 1 curations.
Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy.
2024-10-10, Cell Reports (10.1016/j.celrep.2024.114848) (online)Olivia M Osborne, Manav Daftari, Oandy Naranjo, Adarsh N Johar, Samantha Brooks, Brett M Colbert, Silvia Torices, Elizabeth Lewis, Jet Sendaydiego, Gillian Drexler, Malek Bashti, Alexander V Margetts, Luis M Tuesta, Christian Mason, Daniel Bilbao, Regina Vontell, Anthony J Griswold, Derek M Dykxhoorn, and Michal Toborek (?)
Ischemic stroke and cerebral amyloid angiopathy (CAA) pose significant challenges in an aging population, particularly in post-stroke recovery. Using the 5xFAD mouse model, we explore the relationship between CAA, ischemic stroke, and tissue recovery. We hypothesize that amyloid-beta accumulation worsens stroke outcomes by inducing blood-brain barrier (BBB) dysfunction, leading to impaired neurogenesis. Our findings show that CAA exacerbates stroke outcomes, with mice exhibiting constricted BBB microvessels, reduced cerebral blood flow, and impaired tissue recovery. Transcriptional analysis shows that endothelial cells and neural progenitor cells (NPCs) in the hippocampus exhibit differential gene expression in response to CAA and stroke, specifically targeting the phosphatidylinositol 3-kinase (PI3K) pathway. In vitro experiments with human NPCs validate these findings, showing that disruption of the CXCL12-PIK3C2A-CREB3L2 axis impairs neurogenesis. Notably, PI3K pathway activation restores neurogenesis, highlighting a potential therapeutic approach. These results suggest that CAA combined with stroke induces microvascular dysfunction and aberrant neurogenesis through this specific pathway.
Added on Monday, November 11, 2024. Currently included in 1 curations.
Single-neuron representations of odours in the human brain.
2024-10-09, Nature (10.1038/s41586-024-08016-5) (online)Valeri Borger, Sina Mackay, Florian Mormann, Marcel S Kehl, Kathrin Ohla, Matthias Schneider, Rainer Surges, and Marc Spehr (?)
Olfaction is a fundamental sensory modality that guides animal and human behaviour. However, the underlying neural processes of human olfaction are still poorly understood at the fundamental-that is, the single-neuron-level. Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and identification task. We identified odour-modulated neurons within the piriform cortex, amygdala, entorhinal cortex and hippocampus. In each of these regions, neuronal firing accurately encodes odour identity. Notably, repeated odour presentations reduce response firing rates, demonstrating central repetition suppression and habituation. Different medial temporal lobe regions have distinct roles in odour processing, with amygdala neurons encoding subjective odour valence, and hippocampal neurons predicting behavioural odour identification performance. Whereas piriform neurons preferably encode chemical odour identity, hippocampal activity reflects subjective odour perception. Critically, we identify that piriform cortex neurons reliably encode odour-related images, supporting a multimodal role of the human piriform cortex. We also observe marked cross-modal coding of both odours and images, especially in the amygdala and piriform cortex. Moreover, we identify neurons that respond to semantically coherent odour and image information, demonstrating conceptual coding schemes in olfaction. Our results bridge the long-standing gap between animal models and non-invasive human studies and advance our understanding of odour processing in the human brain by identifying neuronal odour-coding principles, regional functional differences and cross-modal integration.
Added on Monday, November 11, 2024. Currently included in 1 curations.
Domain-selective and sex-dependent regulation of learning and memory in mice by GIRK channel activity in CA1 pyramidal neurons of the dorsal hippocampus.
2024-10-07, Learning & memory (Cold Spring Harbor, N.Y.) (10.1101/lm.054022.124) (online)Kevin Wickman, Haichang Luo, McKinzie Frederick, Ezequiel Marron Fernandez de Velasco, Jenna Osterlund Oltmanns, and Courtney Wright (?)
G protein-gated inwardly rectifying K (GIRK) channels mediate the postsynaptic inhibitory effect of many neurotransmitters in the hippocampus and are implicated in neurological disorders characterized by cognitive deficits. Here, we show that enhancement or suppression of GIRK channel activity in dorsal CA1 pyramidal neurons disrupted novel object recognition in mice, without impacting open field activity or avoidance behavior. Contextual fear learning was also unaffected, but extinction of contextual fear was disrupted by suppression of GIRK channel activity in male mice. Thus, the strength of GIRK channel activity in dorsal CA1 pyramidal neurons regulates select cognitive task performance in mice.
Added on Monday, November 11, 2024. Currently included in 1 curations.
Psilocybin reduces functional correlation and the encoding of spatial information by neurons in mouse retrosplenial cortex.
2024-10-04, The European journal of neuroscience (10.1111/ejn.16558) (online)Victorita E Ivan, David P Tomàs-Cuesta, Ingrid M Esteves, Artur Luczak, Majid Mohajerani, Bruce L McNaughton, and Aaron J Gruber (?)
Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place-related activity across trials decreased. Psilocybin also reduced the functional correlation among simultaneously recorded neurons. The 5-HTR (serotonin 2A receptor) antagonist ketanserin blocked these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics.
Added on Monday, November 11, 2024. Currently included in 1 curations.
Dopamine-mediated formation of a memory module in the nucleus accumbens for goal-directed navigation.
2024-09-27, Nature Neuroscience (10.1038/s41593-024-01770-9) (online)Hyung-Bae Kwon, Kanghoon Jung, Sarah Krüssel, Sooyeon Yoo, Myungmo An, Benjamin Burke, Nicholas Schappaugh, Youngjin Choi, Zirong Gu, Seth Blackshaw, and Rui M Costa (?)
Spatial memories guide navigation efficiently toward desired destinations. However, the neuronal and circuit mechanisms underlying the encoding of goal locations and its translation into goal-directed navigation remain unclear. Here we demonstrate that mice rapidly form a spatial memory of a shelter during shelter experiences, guiding escape behavior toward the goal location-a shelter-when under threat. Dopaminergic neurons in the ventral tegmental area and their projection to the nucleus accumbens (NAc) encode safety signals associated with the shelter. Optogenetically induced phasic dopamine signals are sufficient to create a place memory that directs escape navigation. Converging dopaminergic and hippocampal glutamatergic inputs to the NAc mediate the formation of a goal-related memory within a subpopulation of NAc neurons during shelter experiences. Artificial co-activation of this goal-related NAc ensemble with neurons in the dorsal periaqueductal gray was sufficient to trigger memory-guided, rather than random, escape behavior. These findings provide causal evidence of cognitive circuit modules linking memory with goal-directed action.
Added on Friday, October 4, 2024. Currently included in 2 curations.
Coordinated NREM sleep oscillations among hippocampal subfields modulate synaptic plasticity in humans.
2024-10-01, Communications Biology (10.1038/s42003-024-06941-9) (online)Zhipeng Li, Jing Wang, Chongyang Tang, Peng Wang, Peng Ren, Siyang Li, Liye Yi, Qiuyi Liu, Lili Sun, Kaizhou Li, Wencai Ding, Hongbo Bao, Lifen Yao, Meng Na, Guoming Luan, and Xia Liang (?)
The integration of hippocampal oscillations during non-rapid eye movement (NREM) sleep is crucial for memory consolidation. However, how cardinal sleep oscillations bind across various subfields of the human hippocampus to promote information transfer and synaptic plasticity remains unclear. Using human intracranial recordings from 25 epilepsy patients, we find that hippocampal subfields, including DG/CA3, CA1, and SUB, all exhibit significant delta and spindle power during NREM sleep. The DG/CA3 displays strong coupling between delta and ripple oscillations with all the other hippocampal subfields. In contrast, the regions of CA1 and SUB exhibit more precise coordination, characterized by event-level triple coupling between delta, spindle, and ripple oscillations. Furthermore, we demonstrate that the synaptic plasticity within the hippocampal circuit, as indexed by delta-wave slope, is linearly modulated by spindle power. In contrast, ripples act as a binary switch that triggers a sudden increase in delta-wave slope. Overall, these results suggest that different subfields of the hippocampus regulate one another through diverse layers of sleep oscillation synchronization, collectively facilitating information processing and synaptic plasticity during NREM sleep.
Added on Friday, October 4, 2024. Currently included in 1 curations.
Large-Scale Mechanistic Models of Brain Circuits with Biophysically and Morphologically Detailed Neurons.
2024-10-02, The Journal of neuroscience : the official journal of the Society for Neuroscience (10.1523/JNEUROSCI.1236-24.2024) (online)Salvador Dura-Bernal, Beatriz Herrera, Carmen Lupascu, Brianna M Marsh, Daniela Gandolfi, Addolorata Marasco, Samuel Neymotin, Armando Romani, Sergio Solinas, Maxim Bazhenov, Etay Hay, Michele Migliore, Michael Reinmann, and Anton Arkhipov (?)
Understanding the brain requires studying its multiscale interactions from molecules to networks. The increasing availability of large-scale datasets detailing brain circuit composition, connectivity, and activity is transforming neuroscience. However, integrating and interpreting this data remains challenging. Concurrently, advances in supercomputing and sophisticated modeling tools now enable the development of highly detailed, large-scale biophysical circuit models. These mechanistic multiscale models offer a method to systematically integrate experimental data, facilitating investigations into brain structure, function, and disease. This review, based on a Society for Neuroscience 2024 MiniSymposium, aims to disseminate recent advances in large-scale mechanistic modeling to the broader community. It highlights (1) examples of current models for various brain regions developed through experimental data integration; (2) their predictive capabilities regarding cellular and circuit mechanisms underlying experimental recordings (e.g., membrane voltage, spikes, local-field potential, electroencephalography/magnetoencephalography) and brain function; and (3) their use in simulating biomarkers for brain diseases like epilepsy, depression, schizophrenia, and Parkinson's, aiding in understanding their biophysical underpinnings and developing novel treatments. The review showcases state-of-the-art models covering hippocampus, somatosensory, visual, motor, auditory cortical, and thalamic circuits across species. These models predict neural activity at multiple scales and provide insights into the biophysical mechanisms underlying sensation, motor behavior, brain signals, neural coding, disease, pharmacological interventions, and neural stimulation. Collaboration with experimental neuroscientists and clinicians is essential for the development and validation of these models, particularly as datasets grow. Hence, this review aims to foster interest in detailed brain circuit models, leading to cross-disciplinary collaborations that accelerate brain research.
Added on Friday, October 4, 2024. Currently included in 1 curations.
Neuron-Glial Interactions: Implications for Plasticity, Behavior, and Cognition.
2024-10-02, The Journal of neuroscience : the official journal of the Society for Neuroscience (10.1523/JNEUROSCI.1231-24.2024) (online)Mauricio Rangel-Gomez, Cristina M Alberini, Benjamin Deneen, Gabrielle T Drummond, Tiina Manninen, Mriganka Sur, and Aleksandra Vicentic (?)
The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, to include a diversity of other functions, such as regulation of complex behaviors. Astrocytes, the most abundant glial cells in the central nervous system (CNS), have been shown to modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling and behavioral functions. Contemporary studies further highlight astrocytes' involvement in complex cognitive functions. For instance, inhibiting astrocytes in the hippocampus can lead to memory deficits, suggesting their integral role in memory processes. Moreover, astrocytic calcium activity and astrocyte-neuron metabolic coupling have been linked to changes in synaptic strength and learning. Microglia, another type of glial cell, also extend beyond their supportive roles, contributing to learning and memory processes, with microglial reductions impacting these functions in a developmentally dependent manner. Oligodendrocytes, traditionally thought to have limited roles postdevelopment, are now recognized for their activity-dependent modulation of myelination and plasticity, thus influencing behavioral responses. Recent advancements in technology and computational modeling have expanded our understanding of glial functions, particularly how astrocytes influence neuronal circuits and behaviors. This review underscores the importance of glial cells in CNS functions and the need for further research to unravel the complexities of neuron-glia interactions, the impact of these interactions on brain functions, and potential implications for neurological diseases.
Added on Friday, October 4, 2024. Currently included in 1 curations.
Human hippocampal and entorhinal neurons encode the temporal structure of experience.
2024-09-25, Nature (10.1038/s41586-024-07973-1) (online)Pawel Tacikowski, Güldamla Kalender, Davide Ciliberti, and Itzhak Fried (?)
Extracting the underlying temporal structure of experience is a fundamental aspect of learning and memory that allows us to predict what is likely to happen next. Current knowledge about the neural underpinnings of this cognitive process in humans stems from functional neuroimaging research. As these methods lack direct access to the neuronal level, it remains unknown how this process is computed by neurons in the human brain. Here we record from single neurons in individuals who have been implanted with intracranial electrodes for clinical reasons, and show that human hippocampal and entorhinal neurons gradually modify their activity to encode the temporal structure of a complex image presentation sequence. This representation was formed rapidly, without providing specific instructions to the participants, and persisted when the prescribed experience was no longer present. Furthermore, the structure recovered from the population activity of hippocampal-entorhinal neurons closely resembled the structural graph defining the sequence, but at the same time, also reflected the probability of upcoming stimuli. Finally, learning of the sequence graph was related to spontaneous, time-compressed replay of individual neurons' activity corresponding to previously experienced graph trajectories. These findings demonstrate that neurons in the hippocampus and entorhinal cortex integrate the 'what' and 'when' information to extract durable and predictive representations of the temporal structure of human experience.
Added on Friday, September 27, 2024. Currently included in 1 curations.
Pronouns reactivate conceptual representations in human hippocampal neurons.
2024-09-26, Science (New York, N.Y.) (10.1126/science.adr2813) (online)D E Dijksterhuis, M W Self, J K Possel, J C Peters, E C W van Straaten, S Idema, J C Baaijen, S M A van der Salm, E J Aarnoutse, N C E van Klink, P van Eijsden, S Hanslmayr, R Chelvarajah, F Roux, L D Kolibius, V Sawlani, D T Rollings, S Dehaene, and P R Roelfsema (?)
During discourse comprehension, every new word adds to an evolving representation of meaning that accumulates over consecutive sentences and constrains the next words. To minimize repetition and utterance length, languages use pronouns, like the word "she," to refer to nouns and phrases that were previously introduced. It has been suggested that language comprehension requires that pronouns activate the same neuronal representations as the nouns themselves. We recorded from individual neurons in the human hippocampus during a reading task. Cells that were selective to a particular noun were later reactivated by pronouns that refer to the cells' preferred noun. These results imply that concept cells contribute to a rapid and dynamic semantic memory network that is recruited during language comprehension.
Added on Friday, September 27, 2024. Currently included in 1 curations.
Local wakefulness-like activity of layer 5 cortex under general anaesthesia.
2024-09-24, The Journal of Physiology (10.1113/JP286417) (online)Guglielmo Foffani, Jesús Pardo-Valencia, Miryam Moreno-Gomez, Noelia Mercado, Beatriz Pro, Claudia Ammann, and Desire Humanes-Valera (?)
Consciousness, defined as being aware of and responsive to one's surroundings, is characteristic of normal waking life and typically is lost during sleep and general anaesthesia. The traditional view of consciousness as a global brain state has evolved toward a more sophisticated interplay between global and local states, with the presence of local sleep in the awake brain and local wakefulness in the sleeping brain. However, this interplay is not clear for general anaesthesia, where loss of consciousness was recently suggested to be associated with a global state of brain-wide synchrony that selectively involves layer 5 cortical pyramidal neurons across sensory, motor and associative areas. According to this global view, local wakefulness of layer 5 cortex should be incompatible with deep anaesthesia, a hypothesis that deserves to be scrutinised with causal manipulations. Here, we show that unilateral chemogenetic activation of layer 5 pyramidal neurons in the sensorimotor cortex of isoflurane-anaesthetised mice induces a local state transition from slow-wave activity to tonic firing in the transfected hemisphere. This wakefulness-like activity dramatically disrupts layer 5 interhemispheric synchrony with mirror-image locations in the contralateral hemisphere, but does not reduce the level of unconsciousness under deep anaesthesia, nor in the transitions to/from anaesthesia. Global layer 5 synchrony may thus be a sufficient condition for anaesthesia-induced unconsciousness, but is not a necessary one, at least under isoflurane anaesthesia. Local wakefulness-like activity of layer 5 cortex can be induced and maintained under deep anaesthesia, encouraging further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness. KEY POINTS: The neural correlates of consciousness have evolved from global brain states to a nuanced interplay between global and local states, evident in terms of local sleep in awake brains and local wakefulness in sleeping brains. The concept of local wakefulness remains unclear for general anaesthesia, where the loss of consciousness has been recently suggested to involve brain-wide synchrony of layer 5 cortical neurons. We found that local wakefulness-like activity of layer 5 cortical can be chemogenetically induced in anaesthetised mice without affecting the depth of anaesthesia or the transitions to and from unconsciousness. Global layer 5 synchrony may thus be a sufficient but not necessary feature for the unconsciousness induced by general anaesthesia. Local wakefulness-like activity of layer 5 neurons is compatible with general anaesthesia, thus promoting further investigation into the local vs. global aspects of anaesthesia-induced unconsciousness.
Added on Wednesday, September 25, 2024. Currently included in 1 curations.
Repetition dynamically and rapidly increases cortical, but not hippocampal, offline reactivation.
2024-09-24, Proceedings of the National Academy of Sciences of the United States of America (10.1073/pnas.2405929121) (online)Wangjing Yu, Asieh Zadbood, Avi J H Chanales, and Lila Davachi (?)
No sooner is an experience over than its neural representation begins to be transformed through memory reactivation during offline periods. The lion's share of prior research has focused on understanding offline reactivation within the hippocampus. However, it is hypothesized that consolidation processes involve offline reactivation in cortical regions as well as coordinated reactivation in the hippocampus and cortex. Using fMRI, we presented novel and repeated paired associates to participants during encoding and measured offline memory reactivation for those events during an immediate post-encoding rest period. post-encoding reactivation frequency of repeated and once-presented events did not differ in the hippocampus. However, offline reactivation in widespread cortical regions and hippocampal-cortical coordinated reactivation were significantly enhanced for repeated events. These results provide evidence that repetition might facilitate the distribution of memory representations across cortical networks, a hallmark of systems-level consolidation. Interestingly, we found that offline reactivation frequency in both hippocampus and cortex explained variance in behavioral success on an immediate associative recognition test for the once-presented information, potentially indicating a role of offline reactivation in maintaining these novel, weaker, memories. Together, our findings highlight that endogenous offline reactivation can be robustly and significantly modulated by study repetition.
Added on Wednesday, September 25, 2024. Currently included in 1 curations.
Distinct ventral hippocampal inhibitory microcircuits regulating anxiety and fear behaviors.
2024-09-19, Nature Communications (10.1038/s41467-024-52466-4) (online)Kaizhen Li, Konstantinos Koukoutselos, Masanori Sakaguchi, and Stéphane Ciocchi (?)
In emotion research, anxiety and fear have always been interconnected, sharing overlapping brain structures and neural circuitry. Recent investigations, however, have unveiled parallel long-range projection pathways originating from the ventral hippocampus, shedding light on their distinct roles in anxiety and fear. Yet, the mechanisms governing the emergence of projection-specific activity patterns to mediate different negative emotions remain elusive. Here, we show a division of labor in local GABAergic inhibitory microcircuits of the ventral hippocampus, orchestrating the activity of subpopulations of pyramidal neurons to shape anxiety and fear behaviors in mice. These findings offer a comprehensive insight into how distinct inhibitory microcircuits are dynamically engaged to encode different emotional states.
Added on Saturday, September 21, 2024. Currently included in 1 curations.
Daily oscillations of neuronal membrane capacitance.
2024-09-17, Cell Reports (10.1016/j.celrep.2024.114744) (online)Daniel Severin, Cristián Moreno, Trinh Tran, Christian Wesselborg, Sofia Shirley, Altagracia Contreras, Alfredo Kirkwood, and Jorge Golowasch (?)
Capacitance of biological membranes is determined by the properties of the lipid portion of the membrane as well as the morphological features of a cell. In neurons, membrane capacitance is a determining factor of synaptic integration, action potential propagation speed, and firing frequency due to its direct effect on the membrane time constant. Besides slow changes associated with increased morphological complexity during postnatal maturation, neuronal membrane capacitance is considered a stable, non-regulated, and constant magnitude. Here we report that, in two excitatory neuronal cell types, pyramidal cells of the mouse primary visual cortex and granule cells of the hippocampus, the membrane capacitance significantly changes between the start and the end of a daily light-dark cycle. The changes are large, nearly 2-fold in magnitude in pyramidal cells, but are not observed in cortical parvalbumin-expressing inhibitory interneurons. Consistent with daily capacitance fluctuations, the time window for synaptic integration also changes in pyramidal cells.
Curator note
As the authors point out, the conventional wisdom is that capacitance is more or less stable for neurons. But changes to membrane capacitance affect the membrane time constant, and this in turn affects synaptic integration.
It allows neurons to "learn" better at certain times of day!
It allows neurons to "learn" better at certain times of day!
Added on Saturday, September 21, 2024. Currently included in 2 curations.
Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.
2024-09-12, Scientific Reports (10.1038/s41598-024-71440-0) (online)Yoshihiro Chadani, Ryoko Fujito, Naohiro Kimura, Ryo Kawai, Tetsuo Kashibayashi, Ryuichi Takahashi, Hideki Kanemoto, Kazunari Ishii, Kenji Tagai, Shunichiro Shinagawa, Manabu Ikeda, and Hiroaki Kazui (?)
In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.
Added on Friday, September 13, 2024. Currently included in 1 curations.
Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer's disease.
2024-09-12, eLife (10.7554/eLife.95412) (online)Felix Michaud, Ruggiero Francavilla, Dimitry Topolnik, Parisa Iloun, Suhel Tamboli, Frederic Calon, and Lisa Topolnik (?)
Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of I-S3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.
Added on Friday, September 13, 2024. Currently included in 1 curations.
Giant pyramidal neurons of the primary motor cortex express vasoactive intestinal polypeptide (VIP), a known marker of cortical interneurons.
2024-09-11, Scientific Reports (10.1038/s41598-024-71637-3) (online)Sadaf Teymornejad, Katrina H Worthy, Marcello G P Rosa, and Nafiseh Atapour (?)
Vasoactive intestinal polypeptide (VIP) is known to be present in a subclass of cortical interneurons. Here, using three different antibodies, we demonstrate that VIP is also present in the giant layer 5 pyramidal (Betz) neurons which are characteristic of the limb and axial representations of the marmoset primary motor cortex (cytoarchitectural area 4ab). No VIP staining was observed in smaller layer 5 pyramidal cells present in the primary motor facial representation (cytoarchitectural area 4c), or in the premotor cortex (e.g. the caudal subdivision of the dorsal premotor cortex, A6DC), indicating the selective expression of VIP in Betz cells. VIP in Betz cells was colocalized with neuronal specific marker (NeuN) and a calcium-binding protein parvalbumin (PV). PV also intensely labelled axon terminals surrounding Betz cell somata. VIP-positive interneurons were more abundant in the superficial cortical layers and constituted about 5-7% of total cortical neurons, with the highest density observed in area 4c. Our results demonstrate the expression of VIP in the largest excitatory neurons of the primate cortex, which may offer new functional insights into the role of VIP in the brain, and provide opportunities for genetic manipulation of Betz cells.
Added on Wednesday, September 11, 2024. Currently included in 1 curations.
Development of Neural Cells and Spontaneous Neural Activities in Engineered Brain-Like Constructs for Transplantation.
2024-09-10, Advanced healthcare materials (10.1002/adhm.202401419) (online)Ke Gai, Mengliu Yang, Wei Chen, Chenyujun Hu, Xiao Luo, Austin Smith, Caizhe Xu, Hefeng Zhang, Xiang Li, Wei Shi, Wei Sun, Feng Lin, and Yu Song (?)
Stem cell transplantation has demonstrated efficacy in treating neurological disorders by generating functional cells and secreting beneficial factors. However, challenges remain for current cell suspension injection therapy, including uncontrollable cell distribution, the potential for tumor formation, and limited ability to treat spatial defects. Therefore, implants with programmable cell development, tailored 3D structure, and functionalized biomaterials have the potential to both control cell distribution and reduce or heal spatial defects. Here, a biomimetic material system comprising gelatin, alginate, and fibrinogen has been developed for neural progenitor cell constructs using 3D printing. The resulting constructs exhibit excellent formability, stability, and developmental functions in vitro, as well as biocompatibility and integration into the hippocampus in vivo. The controllability, reproducibility, and material composition of the constructs show potential for use in personalized stem cell-based therapies for defective neurological disorders, neural development research, disease modeling, and organoid-derived intelligent systems.
Added on Tuesday, September 10, 2024. Currently included in 1 curations.
Organizing the coactivity structure of the hippocampus from robust to flexible memory.
2024-09-05, Science (New York, N.Y.) (10.1126/science.adk9611) (online)Andrew Sharott, Giuseppe P Gava, Laura Lefèvre, Tabitha Broadbelt, Stephen B McHugh, Vítor Lopes-Dos-Santos, Demi Brizee, Katja Hartwich, Hanna Sjoberg, Pavel V Perestenko, Robert Toth, and David Dupret (?)
New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the mouse hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons in the superficial sublayer of the CA1 stratum pyramidale to whole-population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to meet memory demands.
Added on Friday, September 6, 2024. Currently included in 1 curations.
Blockade of dopamine D3 receptors improves hippocampal synaptic function and rescues age-related cognitive phenotype.
2024-09-05, Aging Cell (10.1111/acel.14291) (online)Maria Rosaria Tropea, Marcello Melone, Domenica Donatella Li Puma, Valeria Vacanti, Giuseppe Aceto, Bruno Bandiera, Roberta Carmela Trovato, Sebastiano Alfio Torrisi, Gian Marco Leggio, Agostino Palmeri, Marcello D'Ascenzo, Fiorenzo Conti, Claudio Grassi, and Daniela Puzzo (?)
Dopamine D3 receptors (D3Rs) modulate neuronal activity in several brain regions including the hippocampus. Although previous studies reported that blocking D3Rs exerts pro-cognitive effects, their involvement in hippocampal synaptic function and memory in the healthy and aged brain has not been thoroughly investigated. We demonstrated that in adult wild type (WT) mice, D3R pharmacological blockade or genetic deletion as in D3 knock out (KO) mice, converted the weak form of long-term potentiation (LTP1) into the stronger long-lasting LTP (LTP2) via the cAMP/PKA pathway, and allowed the formation of long-term memory. D3R effects were mainly mediated by post-synaptic mechanisms as their blockade enhanced basal synaptic transmission (BST), AMPAR-mediated currents, mEPSC amplitude, and the expression of the post-synaptic proteins PSD-95, phospho(p)GluA1 and p-CREB. Consistently, electron microscopy revealed a prevalent expression of D3Rs in post-synaptic dendrites. Interestingly, with age, D3Rs decreased in axon terminals while maintaining their levels in post-synaptic dendrites. Indeed, in aged WT mice, blocking D3Rs reversed the impairment of LTP, BST, memory, post-synaptic protein expression, and PSD length. Notably, aged D3-KO mice did not exhibit synaptic and memory deficits. In conclusion, we demonstrated the fundamental role of D3Rs in hippocampal synaptic function and memory, and their potential as a therapeutic target to counteract the age-related hippocampal cognitive decline.
Added on Friday, September 6, 2024. Currently included in 1 curations.
Inhibitory plasticity supports replay generalization in the hippocampus.
2024-09-03, Nature Neuroscience (10.1038/s41593-024-01745-w) (online)Attila Losonczy, Zhenrui Liao, Satoshi Terada, Ivan Georgiev Raikov, Darian Hadjiabadi, Miklos Szoboszlay, and Ivan Soltesz (?)
Memory consolidation assimilates recent experiences into long-term memory. This process requires the replay of learned sequences, although the content of these sequences remains controversial. Recent work has shown that the statistics of replay deviate from those of experience: stimuli that are experientially salient may be either recruited or suppressed from sharp-wave ripples. In this study, we found that this phenomenon can be explained parsimoniously and biologically plausibly by a Hebbian spike-time-dependent plasticity rule at inhibitory synapses. Using models at three levels of abstraction-leaky integrate-and-fire, biophysically detailed and abstract binary-we show that this rule enables efficient generalization, and we make specific predictions about the consequences of intact and perturbed inhibitory dynamics for network dynamics and cognition. Finally, we use optogenetics to artificially implant non-generalizable representations into the network in awake behaving mice, and we find that these representations also accumulate inhibition during sharp-wave ripples, experimentally validating a major prediction of our model. Our work outlines a potential direct link between the synaptic and cognitive levels of memory consolidation, with implications for both normal learning and neurological disease.
Added on Wednesday, September 4, 2024. Currently included in 1 curations.
Conjunctive processing of spatial border and locomotion in retrosplenial cortex during spatial navigation.
2024-08-31, The Journal of Physiology (10.1113/JP286434) (online)Hao Sun, Ruolan Cai, Rui Li, Mingxuan Li, Lixia Gao, and Xinjian Li (?)
Spatial information and dynamic locomotor behaviours are equally important for achieving locomotor goals during spatial navigation. However, it remains unclear how spatial and locomotor information is integrated during the processing of self-initiated spatial navigation. Anatomically, the retrosplenial cortex (RSC) has reciprocal connections with brain regions related to spatial processing, including the hippocampus and para-hippocampus, and also receives inputs from the secondary motor cortex. In addition, RSC is functionally associated with allocentric and egocentric spatial targets and head-turning. So, RSC may be a critical region for integrating spatial and locomotor information. In this study, we first examined the role of RSC in spatial navigation using the Morris water maze and found that mice with inactivated RSC took a longer time and distance to reach their destination. Then, by imaging neuronal activity in freely behaving mice within two open fields of different sizes, we identified a large proportion of border cells, head-turning cells and locomotor speed cells in the superficial layer of RSC. Interestingly, some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals. Furthermore, these conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigator scenes using the border, turning and positive-speed conjunctive cells. Our study reveals that the RSC is an important conjunctive brain region that processes spatial and locomotor information during spatial navigation. KEY POINTS: Retrosplenial cortex (RSC) is indispensable during spatial navigation, which was displayed by the longer time and distance of mice to reach their destination after the inactivation of RSC in a water maze. The superficial layer of RSC has a larger population of spatial-related border cells, and locomotion-related head orientation and speed cells; however, it has few place cells in two-dimensional spatial arenas. Some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals, and the conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigation scenes. Our study reveals that the RSC is an important conjunctive brain region that processes both spatial and locomotor information during spatial navigation.
Added on Tuesday, September 3, 2024. Currently included in 1 curations.
Propagation of sharp wave-ripple activity in the mouse hippocampal CA3 subfield in vitro.
2024-08-31, The Journal of Physiology (10.1113/JP285671) (online)Richard Kempter, Natalie Schieferstein, Ana Del Toro, Roberta Evangelista, Barbara Imbrosci, Aarti Swaminathan, Dietmar Schmitz, and Nikolaus Maier (?)
Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation - the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus. SPW-Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW-Rs in CA3, we recorded from mouse hippocampal slices using multi-electrode arrays and patch-clamp electrodes. We characterized extracellular and intracellular correlates of SPW-Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW-Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch-clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW-Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW-Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells. KEY POINTS: Hippocampal sharp waves are considered important for memory consolidation; therefore, it is of interest to understand the mechanisms of their generation and propagation. Here, we used two different approaches to study the propagation of sharp waves in mouse CA3 in vitro: multi-electrode arrays and multiple single-cell recordings. We find a preferred direction of propagation of sharp waves from CA3c toward CA3a - both in the local field potential and in sharp wave-associated excitatory and inhibitory synaptic activity. The speed of sharp wave propagation is consistent with the speed of action potential propagation along the axons of CA3 pyramidal neurons. These new insights into the dynamics of sharp waves in the CA3 network will inform future experiments and theoretical models of sharp-wave generation mechanisms.
Added on Tuesday, September 3, 2024. Currently included in 1 curations.
Hippocampal storage and recall of neocortical "What"-"Where" representations.
2024-09-02, Hippocampus (10.1002/hipo.23636) (online)Edmund T Rolls, Chenfei Zhang, and Jianfeng Feng (?)
A key question for understanding the function of the hippocampus in memory is how information is recalled from the hippocampus to the neocortex. This was investigated in a neuronal network model of the hippocampal system in which "What" and "Where" neuronal firing rate vectors were applied to separate neocortical modules, which then activated entorhinal cortex "What" and "Where" modules, then the dentate gyrus, then CA3, then CA1, then the entorhinal cortex, and then the backprojections to the neocortex. A rate model showed that the whole system could be trained to recall "Where" in the neocortex from "What" applied as a retrieval cue to the neocortex, and could in principle be trained up towards the theoretical capacity determined largely by the number of synapses onto any one neuron divided by the sparseness of the representation. The trained synaptic weights were then imported into an integrate-and-fire simulation of the same architecture, which showed that the time from presenting a retrieval cue to a neocortex module to recall the whole memory in the neocortex is approximately 100 ms. This is sufficiently fast for the backprojection synapses to be trained onto the still active neocortical neurons during storage of the episodic memory, and this is needed for recall to operate correctly to the neocortex. These simulations also showed that the long loop neocortex-hippocampus-neocortex that operates continuously in time may contribute to complete recall in the neocortex; but that this positive feedback long loop makes the whole dynamical system inherently liable to a pathological increase in neuronal activity. Important factors that contributed to stability included increased inhibition in CA3 and CA1 to keep the firing rates low; and temporal adaptation of the neuronal firing and of active synapses, which are proposed to make an important contribution to stabilizing runaway excitation in cortical circuits in the brain.
Added on Tuesday, September 3, 2024. Currently included in 1 curations.
Differential role of NMDA receptors in hippocampal-dependent spatial memory and plasticity in juvenile male and female rats.
2024-08-15, Hippocampus (10.1002/hipo.23631) (online)Nisha Rajan Narattil, and Mouna Maroun (?)
Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long-term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation. Given the crucial role of the hippocampus in spatial memory processing, it has been observed that spatial memory abilities continue to develop as the hippocampus matures, particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is crucial for the induction of activity-dependent synaptic plasticity and spatial memory formation in both rodents and humans. Although extensive evidence shows the role of NMDA receptors (NMDAr) in spatial memory and synaptic plasticity, the studies addressing the role of NMDAr in spatial memory of juveniles are sparse and mostly limited to adult males. In the present study, we, therefore, aimed to investigate the effects of systemic NMDAr blockade by the MK-801 on spatial memory (novel object location memory, OLM) and hippocampal plasticity in the form of long-term potentiation (LTP) of both male and female juvenile rats. Our results show the sex-dimorphic role of NMDAr in spatial memory and plasticity during juvenility, as systemic NMDAr blockade impairs the OLM and LTP in juvenile males without an effect on juvenile females. Taken together, our results demonstrate that spatial memory and hippocampal plasticity are NMDAr-dependent in juvenile males and NMDAr-independent in juvenile females. These sex-specific differences in the mechanisms of spatial memory and plasticity may imply gender-specific treatment for spatial memory disorders even in children.
Added on Monday, August 26, 2024. Currently included in 1 curations.
Perineuronal Nets in the Rat Medial Prefrontal Cortex Alter Hippocampal-Prefrontal Oscillations and Reshape Cocaine Self-Administration Memories.
2024-08-21, The Journal of neuroscience : the official journal of the Society for Neuroscience (10.1523/JNEUROSCI.0468-24.2024) (online)Jereme C Wingert, Jonathan D Ramos, Sebastian X Reynolds, Angela E Gonzalez, R Mae Rose, Deborah M Hegarty, Sue A Aicher, Lydia G Bailey, Travis E Brown, Atheir I Abbas, and Barbara A Sorg (?)
The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.
Added on Monday, August 26, 2024. Currently included in 1 curations.
Egocentric neural representation of geometric vertex in the retrosplenial cortex.
2024-08-21, Nature Communications (10.1038/s41467-024-51391-w)Kyerl Park, Yoonsoo Yeo, Kisung Shin, and Jeehyun Kwag (?)
Egocentric neural representations of environmental features, such as edges and vertices, are important for constructing a geometrically detailed egocentric cognitive map for goal-directed navigation and episodic memory. While egocentric neural representations of edges like egocentric boundary/border cells exist, those that selectively represent vertices egocentrically are yet unknown. Here we report that granular retrosplenial cortex (RSC) neurons in male mice generate spatial receptive fields exclusively near the vertices of environmental geometries during free exploration, termed vertex cells. Their spatial receptive fields occurred at a specific orientation and distance relative to the heading direction of mice, indicating egocentric vector coding of vertex. Removing physical boundaries defining the environmental geometry abolished the egocentric vector coding of vertex, and goal-directed navigation strengthened the egocentric vector coding at the goal-located vertex. Our findings suggest that egocentric vector coding of vertex by granular RSC neurons helps construct an egocentric cognitive map that guides goal-directed navigation.
Added on Friday, August 23, 2024. Currently included in 1 curations.
Repeated exposure to novelty promotes resilience against the amyloid-beta effect through dopaminergic stimulation.
2024-08-15, Psychopharmacology (10.1007/s00213-024-06650-5) (online)Cintia Velázquez-Delgado, Eduardo Hernández-Ortiz, Lucia Landa-Navarro, Miguel Tapia-Rodríguez, Perla Moreno-Castilla, and Federico Bermúdez-Rattoni (?)
The accumulation of beta-amyloid peptide (Aβ) in the forebrain leads to cognitive dysfunction and neurodegeneration in Alzheimer's disease. Studies have shown that individuals with a consistently cognitively active lifestyle are less vulnerable to Aβ toxicity. Recent research has demonstrated that intrahippocampal Aβ can impact catecholaminergic release and spatial memory. Interestingly, exposure to novelty stimuli has been found to stimulate the release of catecholamines in the hippocampus. However, it remains uncertain whether repeated enhancing catecholamine activity can effectively alleviate cognitive impairment in individuals with Alzheimer's disease.
Added on Friday, August 16, 2024. Currently included in 1 curations.
Representations of tactile object location in the retrosplenial cortex.
2023-09-28, Current Biology (10.1016/j.cub.2023.09.019) (online)Andreas Sigstad Lande, Anna Christina Garvert, Nora Cecilie Ebbesen, Sondre Valentin Jordbræk, and Koen Vervaeke (?)
How animals use tactile sensation to detect important objects and remember their location in a world-based coordinate system is unclear. Here, we hypothesized that the retrosplenial cortex (RSC), a key network for contextual memory and spatial navigation, represents the location of objects based on tactile sensation. We studied mice palpating objects with their whiskers while navigating in a tactile virtual reality in darkness. Using two-photon Ca imaging, we discovered that a population of neurons in the agranular RSC signal the location of objects. Responses to objects do not simply reflect the sensory stimulus. Instead, they are highly position, task, and context dependent and often predict the upcoming object before it is within reach. In addition, a large fraction of neurons encoding object location maintain a memory trace of the object's location. These data show that the RSC encodes the location and arrangement of tactile objects in a spatial reference frame.
Added on Thursday, August 15, 2024. Currently included in 1 curations.
Abstract representations emerge in human hippocampal neurons during inference.
2024-08-14, Nature (10.1038/s41586-024-07799-x) (online)Hristos S Courellis, Juri Minxha, Araceli R Cardenas, Daniel L Kimmel, Chrystal M Reed, Taufik A Valiante, C Daniel Salzman, Adam N Mamelak, Stefano Fusi, and Ueli Rutishauser (?)
Humans have the remarkable cognitive capacity to rapidly adapt to changing environments. Central to this capacity is the ability to form high-level, abstract representations that take advantage of regularities in the world to support generalization. However, little is known about how these representations are encoded in populations of neurons, how they emerge through learning and how they relate to behaviour. Here we characterized the representational geometry of populations of neurons (single units) recorded in the hippocampus, amygdala, medial frontal cortex and ventral temporal cortex of neurosurgical patients performing an inferential reasoning task. We found that only the neural representations formed in the hippocampus simultaneously encode several task variables in an abstract, or disentangled, format. This representational geometry is uniquely observed after patients learn to perform inference, and consists of disentangled directly observable and discovered latent task variables. Learning to perform inference by trial and error or through verbal instructions led to the formation of hippocampal representations with similar geometric properties. The observed relation between representational format and inference behaviour suggests that abstract and disentangled representational geometries are important for complex cognition.
Added on Thursday, August 15, 2024. Currently included in 1 curations.
Investigating egocentric tuning in hippocampal CA1 neurons.
2024-08-13, The Journal of neuroscience : the official journal of the Society for Neuroscience (10.1523/JNEUROSCI.0040-24.2024) (online)Jordan Carpenter, Jan Sigurd Blackstad, David Tingley, Valentin A Normand, Edvard I Moser, May-Britt Moser, and Benjamin A Dunn (?)
Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animal's position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false positive rate. When we accounted for false positives by comparing with shuffled data that retain correlations between the animal's direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting false positive rates and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons. This study investigates the relationship between world-centered (allocentric) and self-centered (egocentric) frames of spatial coding in the hippocampus during navigation. Through targeted electrophysiological single-unit recordings in hippocampal CA1 area, complemented by simulations of spatially modulated neurons, we find a compelling lack of support in free-foraging rats for recent proposals that the hippocampus relies on internal egocentric signals in relation to reference points distributed through the environment. Our work reveals that ego-centric signals in CA1 may be strongly biased by stereotypical behavioral patterns. The findings suggest that in free-foraging rodents, the principal framework for location coding is allocentric.
Added on Wednesday, August 14, 2024. Currently included in 1 curations.
Differential stability of task variable representations in retrosplenial cortex.
2024-08-11, Nature Communications (10.1038/s41467-024-51227-7) (online)Michael J. Goard, and Luis M Franco (?)
Cortical neurons store information across different timescales, from seconds to years. Although information stability is variable across regions, it can vary within a region as well. Association areas are known to multiplex behaviorally relevant variables, but the stability of their representations is not well understood. Here, we longitudinally recorded the activity of neuronal populations in the mouse retrosplenial cortex (RSC) during the performance of a context-choice association task. We found that the activity of neurons exhibits different levels of stability across days. Using linear classifiers, we quantified the stability of three task-relevant variables. We find that RSC representations of context and trial outcome display higher stability than motor choice, both at the single cell and population levels. Together, our findings show an important characteristic of association areas, where diverse streams of information are stored with varying levels of stability, which may balance representational reliability and flexibility according to behavioral demands.
Added on Tuesday, August 13, 2024. Currently included in 1 curations.
Selective reactivation of value- and place-dependent information during sharp-wave ripples in the intermediate and dorsal hippocampus.
2024-08-07, Science Advances (10.1126/sciadv.adn0416) (online)Seung-Woo Jin, Hee-Seung Ha, and Inah Lee (?)
Reactivating place cells during sharp-wave ripples in the hippocampus is important for memory consolidation. However, whether hippocampal reactivation is affected by the values of events experienced by the animal is largely unknown. Here, we investigated whether place cells in the dorsal (dHP) and intermediate hippocampus (iHP) of rats are differentially reactivated depending on the value associated with a place during the learning of places associated with higher-value rewards in a T-maze. Place cells in the iHP representing the high-value location were reactivated significantly more frequently than those representing the low-value location, characteristics not observed in the dHP. In contrast, the activities of place cells in the dHP coding the routes leading to high-value locations were replayed more than those in the iHP. Our findings suggest that value-based differential reactivation patterns along the septotemporal axis of the hippocampus may play essential roles in optimizing goal-directed spatial learning for maximal reward.
Added on Thursday, August 8, 2024. Currently included in 1 curations.
Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations.
2024-03-11, Nature Communications (10.1038/s41467-024-46478-3) (online)Chinnakkaruppan Adaikkan, Justin Joseph, Georgios Foustoukos, Jun Wang, Denis Polygalov, Roman Boehringer, Steven J Middleton, Arthur J Y Huang, Li-Huei Tsai, and Thomas J McHugh (?)
The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.
Added on Wednesday, August 7, 2024. Currently included in 1 curations.
Cell-type-specific representation of spatial context in the rat prefrontal cortex.
2024-04-15, iScience (10.1016/j.isci.2024.109743) (online)Hans Brünner, Hoseok Kim, Sofie Ährlund-Richter, Josina Anna van Lunteren, Ana Paula Crestani, Konstantinos Meletis, and Marie Carlén (?)
The ability to represent one's own position in relation to cues, goals, or threats is crucial to successful goal-directed behavior. Using optotagging in knock-in rats expressing Cre recombinase in parvalbumin (PV) neurons (PV-Cre rats), we demonstrate cell-type-specific encoding of spatial and movement variables in the medial prefrontal cortex (mPFC) during goal-directed reward seeking. Single neurons encoded the conjunction of the animal's spatial position and the run direction, referred to as the spatial context. The spatial context was most prominently represented by the inhibitory PV interneurons. Movement toward the reward was signified by increased local field potential (LFP) oscillations in the gamma band but this LFP signature was not related to the spatial information in the neuronal firing. The results highlight how spatial information is incorporated into cognitive operations in the mPFC. The presented PV-Cre line opens the door for expanded research approaches in rats.
Added on Tuesday, August 6, 2024. Currently included in 1 curations.
Adult neurogenesis improves spatial information encoding in the mouse hippocampus.
2024-07-30, Nature Communications (10.1038/s41467-024-50699-x) (online)M Agustina Frechou, Sunaina S Martin, Kelsey D McDermott, Evan A Huaman, Şölen Gökhan, Wolfgang A Tomé, Ruben Coen-Cagli, and J Tiago Gonçalves (?)
Adult neurogenesis is a unique form of neuronal plasticity in which newly generated neurons are integrated into the adult dentate gyrus in a process that is modulated by environmental stimuli. Adult-born neurons can contribute to spatial memory, but it is unknown whether they alter neural representations of space in the hippocampus. Using in vivo two-photon calcium imaging, we find that male and female mice previously housed in an enriched environment, which triggers an increase in neurogenesis, have increased spatial information encoding in the dentate gyrus. Ablating adult neurogenesis blocks the effect of enrichment and lowers spatial information, as does the chemogenetic silencing of adult-born neurons. Both ablating neurogenesis and silencing adult-born neurons decreases the calcium activity of dentate gyrus neurons, resulting in a decreased amplitude of place-specific responses. These findings are in contrast with previous studies that suggested a predominantly inhibitory action for adult-born neurons. We propose that adult neurogenesis improves representations of space by increasing the gain of dentate gyrus neurons and thereby improving their ability to tune to spatial features. This mechanism may mediate the beneficial effects of environmental enrichment on spatial learning and memory.
Added on Wednesday, July 31, 2024. Currently included in 1 curations.
Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types.
2022-11-04, Science (New York, N.Y.) (10.1126/science.abm8797) (online)Cheng Huang, Junjie Luo, Madhuvanthi Kannan, Ganesh Vasan, Mark J Schnitzer, Simon Haziza, Radosław Chrapkiewicz, Jessica A Cardin, and Vincent A Pieribone (?)
Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR. Our indicators enable 0.4- to 1-kilohertz voltage recordings from >50 spiking neurons per field of view in awake mice and ~30-minute continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered brain state-dependent antagonism between neocortical somatostatin-expressing (SST) and vasoactive intestinal peptide-expressing (VIP) interneurons and contributions to hippocampal field potentials from cell ensembles with distinct axonal projections. By combining three mutually compatible indicators, we performed simultaneous triple-population imaging. These approaches will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution.
Added on Wednesday, July 31, 2024. Currently included in 2 curations.
Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy.
2024-07-22, GeroScience (10.1007/s11357-024-01269-y) (online)Steve Horvath, Ezequiel Lacunza, Martina Canatelli Mallat, Enrique L Portiansky, Maria D Gallardo, Robert T Brooke, Priscila Chiavellini, Diana C Pasquini, Mauricio Girard, Marianne Lehmann, Qi Yan, Ake T Lu, Amin Haghani, Juozas Gordevicius, Martin Abba, and Rodolfo G Goya (?)
Several studies have indicated that interrupted epigenetic reprogramming using Yamanaka transcription factors (OSKM) can rejuvenate cells from old laboratory animals and humans. However, the potential of OSKM-induced rejuvenation in brain tissue has been less explored. Here, we aimed to restore cognitive performance in 25.3-month-old female Sprague-Dawley rats using OSKM gene therapy for 39 days. Their progress was then compared with the cognitive performance of untreated 3.5-month-old rats as well as old control rats treated with a placebo adenovector. The Barnes maze test, used to assess cognitive performance, demonstrated enhanced cognitive abilities in old rats treated with OSKM compared to old control animals. In the treated old rats, there was a noticeable trend towards improved spatial memory relative to the old controls. Further, OSKM gene expression did not lead to any pathological alterations within the 39 days. Analysis of DNA methylation following OSKM treatment yielded three insights. First, epigenetic clocks for rats suggested a marginally significant epigenetic rejuvenation. Second, chromatin state analysis revealed that OSKM treatment rejuvenated the methylome of the hippocampus. Third, an epigenome-wide association analysis indicated that OSKM expression in the hippocampus of old rats partially reversed the age-related increase in methylation. In summary, the administration of Yamanaka genes via viral vectors rejuvenates the functional capabilities and the epigenetic landscape of the rat hippocampus.
Added on Wednesday, July 31, 2024. Currently included in 1 curations.
Firing rate adaptation affords place cell theta sweeps, phase precession, and procession.
2024-07-22, eLife (10.7554/eLife.87055) (online)Tianhao Chu, Zilong Ji, Junfeng Zuo, Yuanyuan Mi, Wen-Hao Zhang, Tiejun Huang, Daniel Bush, Neil Burgess, and Si Wu (?)
Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between 'bimodal cells' showing interleaved phase precession and procession, and 'unimodal cells' in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells' firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.
Added on Wednesday, July 31, 2024. Currently included in 1 curations.
Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology.
2024-07-26, Brain (10.1093/brain/awae197) (online)Donna Gift Cabalo, Jordan DeKraker, Jessica Royer, Ke Xie, Shahin Tavakol, Raúl Rodríguez-Cruces, Andrea Bernasconi, Neda Bernasconi, Alexander Weil, Raluca Pana, Birgit Frauscher, Lorenzo Caciagli, Elizabeth Jefferies, Jonathan Smallwood, and Boris C Bernhardt (?)
Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE as well as 60 age and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, on the other hand, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, while hippocampal functional topographies were unaffected. Leveraging MRI proxies of MTL pathology, we furthermore observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic, but again not semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, while episodic processes are supported by a network involving both the hippocampus and neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.
Added on Sunday, July 28, 2024. Currently included in 1 curations.
Functional architecture of intracellular oscillations in hippocampal dendrites.
2024-07-26, Nature Communications (10.1038/s41467-024-50546-z) (online)Zhenrui Liao, Kevin C Gonzalez, Deborah M Li, Catalina M Yang, Donald Holder, Natalie E McClain, Guofeng Zhang, Stephen W Evans, Mariya Chavarha, Jane Simko, Christopher D Makinson, Michael Z Lin, Attila Losonczy, and Adrian Negrean (?)
Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions, report an advancing gradient of dendritic theta phase along the basal-tuft axis, and describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find that spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.
Added on Sunday, July 28, 2024. Currently included in 1 curations.
Memory's gatekeeper: The role of PFC in the encoding of congruent events.
2024-07-17, Proceedings of the National Academy of Sciences of the United States of America (10.1073/pnas.2403648121) (online)Inês C Guerreiro, and Claudia Clopath (?)
Theoretical models conventionally portray the consolidation of memories as a slow process that unfolds during sleep. According to the classical Complementary Learning Systems theory, the hippocampus (HPC) rapidly changes its connectivity during wakefulness to encode ongoing events and create memory ensembles that are later transferred to the prefrontal cortex (PFC) during sleep. However, recent experimental studies challenge this notion by showing that new information consistent with prior knowledge can be rapidly consolidated in PFC during wakefulness and that PFC lesions disrupt the encoding of congruent events in the HPC. The contributions of the PFC to memory encoding have therefore largely been overlooked. Moreover, most theoretical frameworks assume random and uncorrelated patterns representing memories, disregarding the correlations between our experiences. To address these shortcomings, we developed a HPC-PFC network model that simulates interactions between the HPC and PFC during the encoding of a memory (awake stage), and subsequent consolidation (sleeping stage) to examine the contributions of each region to the consolidation of novel and congruent memories. Our results show that the PFC network uses stored memory "schemas" consolidated during previous experiences to identify inputs that evoke congruent patterns of activity, quickly integrate it into its network, and gate which components are encoded in the HPC. More specifically, the PFC uses GABAergic long-range projections to inhibit HPC neurons representing input components correlated with a previously stored memory "schema," eliciting sparse hippocampal activity during exposure to congruent events, as it has been experimentally observed.
Added on Saturday, July 27, 2024. Currently included in 1 curations.
Aberrant hippocampal Ca microwaves following synapsin-dependent adeno-associated viral expression of Ca indicators.
2024-07-23, eLife (10.7554/eLife.93804) (online)Nicola Masala, Manuel Mittag, Eleonora Ambrad Giovannetti, Darik A O'Neil, Fabian J Distler, Peter Rupprecht, Fritjof Helmchen, Rafael Yuste, Martin Fuhrmann, Heinz Beck, Michael Wenzel, and Tony Kelly (?)
Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca-indicator AAV transduction procedures can produce artefactual Ca responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca microwaves, and we provide a potential solution.
Added on Saturday, July 27, 2024. Currently included in 1 curations.
Astrocyte-derived neurons provide excitatory input to the adult striatal circuitry.
2021-08-17, Proceedings of the National Academy of Sciences of the United States of America (10.1073/pnas.2104119118) (online)Matthijs C Dorst, Gilad Silberberg, María Díaz-Moreno, David O Dias, Eduardo L Guimarães, Daniel Holl, Jannis Kalkitsas, and Christian Göritz (?)
Astrocytes have emerged as a potential source for new neurons in the adult mammalian brain. In mice, adult striatal neurogenesis can be stimulated by local damage, which recruits striatal astrocytes into a neurogenic program by suppression of active Notch signaling (J. P. Magnusson et al., 346, 237-241 [2014]). Here, we induced adult striatal neurogenesis in the intact mouse brain by the inhibition of Notch signaling in astrocytes. We show that most striatal astrocyte-derived neurons are confined to the anterior medial striatum, do not express established striatal neuronal markers, and exhibit dendritic spines, which are atypical for striatal interneurons. In contrast to striatal neurons generated during development, which are GABAergic or cholinergic, most adult astrocyte-derived striatal neurons possess distinct electrophysiological properties, constituting the only glutamatergic striatal population. Astrocyte-derived neurons integrate into the adult striatal microcircuitry, both receiving and providing synaptic input. The glutamatergic nature of these neurons has the potential to provide excitatory input to the striatal circuitry and may represent an efficient strategy to compensate for reduced neuronal activity caused by aging or lesion-induced neuronal loss.
Added on Tuesday, July 23, 2024. Currently included in 2 curations.
The microcircuits of striatum in silico.
2020-04-22, Proceedings of the National Academy of Sciences of the United States of America (10.1073/pnas.2000671117) (online)Matthijs C Dorst, J J Johannes Hjorth, Alexander Kozlov, Ilaria Carannante, Johanna Frost Nylén, Robert Lindroos, Yvonne Johansson, Anna Tokarska, Shreyas M Suryanarayana, Gilad Silberberg, Jeanette Hellgren Kotaleski, and Sten Grillner (?)
The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma-dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.
Added on Tuesday, July 23, 2024. Currently included in 2 curations.
Targeting VGLUT2 in Mature Dopamine Neurons Decreases Mesoaccumbal Glutamatergic Transmission and Identifies a Role for Glutamate Co-release in Synaptic Plasticity by Increasing Baseline AMPA/NMDA Ratio.
2018-08-29, Frontiers in Neural Circuits (10.3389/fncir.2018.00064) (online)Maria Papathanou, Meaghan Creed, Matthijs C Dorst, Zisis Bimpisidis, Sylvie Dumas, Hanna Pettersson, Camilla Bellone, Gilad Silberberg, Christian Lüscher, and Åsa Wallén-Mackenzie (?)
Expression of the gene encoding the Vesicular glutamate transporter 2 (VGLUT2) in midbrain dopamine (DA) neurons enables these neurons to co-release glutamate in the nucleus accumbens (NAc), a feature of putative importance to drug addiction. For example, it has been shown that conditional deletion of gene expression within developing DA neurons in mice causes altered locomotor sensitization to addictive drugs, such as amphetamine and cocaine, in adulthood. Alterations in DA neurotransmission in the mesoaccumbal pathway has been proposed to contribute to these behavioral alterations but the underlying molecular mechanism remains largely elusive. Repeated exposure to cocaine is known to cause lasting adaptations of excitatory synaptic transmission onto medium spiny neurons (MSNs) in the NAc, but the putative contribution of VGLUT2-mediated glutamate co-release from the mesoaccumbal projection has never been investigated. In this study, we implemented a tamoxifen-inducible Cre-LoxP strategy to selectively probe VGLUT2 in mature DA neurons of adult mice. Optogenetics-coupled patch clamp analysis in the NAc demonstrated a significant reduction of glutamatergic neurotransmission, whilst behavioral analysis revealed a normal locomotor sensitization to amphetamine and cocaine. When investigating if the reduced level of glutamate co-release from DA neurons caused a detectable post-synaptic effect on MSNs, patch clamp analysis identified an enhanced baseline AMPA/NMDA ratio in DA receptor subtype 1 (DRD1)-expressing accumbal MSNs which occluded the effect of cocaine on synaptic transmission. We conclude that VGLUT2 in mature DA neurons actively contributes to glutamatergic neurotransmission in the NAc, a finding which for the first time highlights VGLUT2-mediated glutamate co-release in the complex mechanisms of synaptic plasticity in drug addiction.
Added on Tuesday, July 23, 2024. Currently included in 1 curations.
Modelling adult neurogenesis in the aging rodent hippocampus: a midlife crisis
2024-06-03, Frontiers in Neuroscience (10.3389/fnins.2024.1416460) (online)Jon I. Arellano, and Pasko Rakic (?)
<abstract><p>Contrary to humans, adult hippocampal neurogenesis in rodents is not controversial. And in the last three decades, multiple studies in rodents have deemed adult neurogenesis essential for most hippocampal functions. The functional relevance of new neurons relies on their distinct physiological properties during their maturation before they become indistinguishable from mature granule cells. Most functional studies have used very young animals with robust neurogenesis. However, this trait declines dramatically with age, questioning its functional relevance in aging animals, a caveat that has been mentioned repeatedly, but rarely analyzed quantitatively. In this meta-analysis, we use data from published studies to determine the critical functional window of new neurons and to model their numbers across age in both mice and rats. Our model shows that new neurons with distinct functional profile represent about 3% of the total granule cells in young adult 3-month-old rodents, and their number decline following a power function to reach less than 1% in middle aged animals and less than 0.5% in old mice and rats. These low ratios pose an important logical and computational caveat to the proposed essential role of new neurons in the dentate gyrus, particularly in middle aged and old animals, a factor that needs to be adequately addressed when defining the relevance of adult neurogenesis in hippocampal function.</p></abstract>
Added on Tuesday, July 2, 2024. Currently included in 1 curations.
Robust variability of grid cell properties within individual grid modules enhances encoding of local space
2024-06-13, bioRxiv (10.1101/2024.02.27.582373) (online) (PDF)William T. Redman, Santiago Acosta-Mendoza, Xue-Xin Wei, and Michael J. Goard (?)
<abstract id="ABS1"><p id="P2">Although grid cells are one of the most well studied functional classes of neurons in the mammalian brain, the assumption that there is a single grid orientation and spacing per grid module has not been carefully tested. We investigate and analyze a recent large-scale recording of medial entorhinal cortex to characterize the presence and degree of heterogeneity of grid properties within individual modules. We find evidence for small, but robust, variability and hypothesize that this property of the grid code could enhance the ability of encoding local spatial information. Performing analysis on synthetic populations of grid cells, where we have complete control over the amount heterogeneity in grid properties, we demonstrate that variability, of a similar magnitude to the analyzed data, leads to significantly decreased decoding error, even when restricted to activity from a single module. Our results highlight how the heterogeneity of the neural response properties may benefit coding and opens new directions for theoretical and experimental analysis of grid cells.</p></abstract>
Added on Tuesday, July 2, 2024. Currently included in 1 curations.
Electrophysiology and Morphology of Human Cortical Supragranular Pyramidal Cells in a Wide Age Range
2024-06-13, bioRxiv (10.1101/2024.06.13.598792) (online) (PDF)Pál Barzó, Ildikó Szöts, Martin Tóth, Éva Adrienn Csajbók, Gábor Molnár, and Gábor Tamás (?)
<abstract id="ABS1"><p id="P2">The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 years of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition and age-related neurodegenerative diseases.</p></abstract>
Added on Tuesday, July 2, 2024. Currently included in 1 curations.
Intrinsic dynamics of randomly clustered networks generate place fields and preplay of novel environments
2024-06-19, bioRxiv (10.1101/2023.10.26.564173) (online) (PDF)Jordan Breffle, Hannah Germaine, Justin D. Shin, Shantanu P. Jadhav, and Paul Miller (?)
<abstract id="ABS1"><p id="P4">During both sleep and awake immobility, hippocampal place cells reactivate time-compressed versions of sequences representing recently experienced trajectories in a phenomenon known as replay. Intriguingly, spontaneous sequences can also correspond to forthcoming trajectories in novel environments experienced later, in a phenomenon known as preplay. Here, we present a model showing that sequences of spikes correlated with the place fields underlying spatial trajectories in both previously experienced and future novel environments can arise spontaneously in neural circuits with random, clustered connectivity rather than pre-configured spatial maps. Moreover, the realistic place fields themselves arise in the circuit from minimal, landmark-based inputs. We find that preplay quality depends on the network’s balance of cluster isolation and overlap, with optimal preplay occurring in small-world regimes of high clustering yet short path lengths. We validate the results of our model by applying the same place field and preplay analyses to previously published rat hippocampal place cell data. Our results show that clustered recurrent connectivity can generate spontaneous preplay and immediate replay of novel environments. These findings support a framework whereby novel sensory experiences become associated with preexisting “pluripotent” internal neural activity patterns.</p></abstract>
Added on Monday, July 1, 2024. Currently included in 1 curations.
Deciphering Early and Progressive Molecular Signatures in Alzheimer’s Disease through Integrated Longitudinal Proteomic and Pathway Analysis in a Rodent Model
2024-06-12, International Journal of Molecular Sciences (10.3390/ijms25126469) (online)Fahd Al-Mulla, Hamad Yadikar, Mubeen A. Ansari, Mohamed Abu-Farha, Shibu Joseph, and Betty T. Thomas (?)
<abstract><p>Alzheimer’s disease (AD), the leading cause of dementia worldwide, remains a challenge due to its complex origin and degenerative character. The need for accurate biomarkers and treatment targets hinders early identification and intervention. To fill this gap, we used a novel longitudinal proteome methodology to examine the temporal development of molecular alterations in the cortex of an intracerebroventricular streptozotocin (ICV-STZ)-induced AD mouse model for disease initiation and progression at one, three-, and six-weeks post-treatment. Week 1 revealed metabolic protein downregulation, such as Aldoa and Pgk1. Week 3 showed increased Synapsin-1, and week 6 showed cytoskeletal protein alterations like Vimentin. The biological pathways, upstream regulators, and functional effects of proteome alterations were dissected using advanced bioinformatics methods, including Ingenuity Pathway Analysis (IPA) and machine learning algorithms. We identified Mitochondrial Dysfunction, Synaptic Vesicle Pathway, and Neuroinflammation Signaling as disease-causing pathways. Huntington’s Disease Signaling and Synaptogenesis Signaling were stimulated while Glutamate Receptor and Calcium Signaling were repressed. IPA also found molecular connections between PPARGC1B and AGT, which are involved in myelination and possible neoplastic processes, and MTOR and AR, which imply mechanistic involvements beyond neurodegeneration. These results help us comprehend AD’s molecular foundation and demonstrate the promise of focused proteomic techniques to uncover new biomarkers and therapeutic targets for AD, enabling personalized medicine.</p></abstract>
Added on Sunday, June 30, 2024. Currently included in 1 curations.
Circadian rapid eye movement sleep expression is associated with brain microstructural integrity in older adults
2024-06-22, Communications Biology (10.1038/s42003-024-06415-y) (online)Michele Deantoni, Mathilde Reyt, Marine Dourte, Stella de Haan, Alexia Lesoinne, Gilles Vandewalle, Christophe Phillips, Christian Berthomier, Pierre Maquet, Vincenzo Muto, Grégory Hammad, Christina Schmidt, and Marion Baillet (?)
<abstract id="Abs1"><p id="Par1">Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.</p></abstract>
Added on Tuesday, June 25, 2024. Currently included in 1 curations.
Navigation & Localization
Curated by Matthijs Dorst, University of Oslo
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Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
Related issues:
2024:9 December 19th, 2024
2024:8 December 11th, 2024
2024:7 December 10th, 2024
2024:6 December 9th, 2024
2024:5 December 3rd, 2024
2024:4 Hippocampus and Rhythm
2024:3 November 23rd, 2024
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Related issues:
2024:9 December 19th, 2024
2024:8 December 11th, 2024
2024:7 December 10th, 2024
2024:6 December 9th, 2024
2024:5 December 3rd, 2024
2024:4 Hippocampus and Rhythm
2024:3 November 23rd, 2024
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