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Neurobiology of Learning and Memory Sep 2021At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this... (Review)
Review
At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.
Topics: Animals; Dentate Gyrus; Hippocampus; Humans; Mossy Fibers, Hippocampal; Neural Pathways; Neurons; Open Field Test; Recognition, Psychology
PubMed: 34214666
DOI: 10.1016/j.nlm.2021.107486 -
Frontiers in Neural Circuits 2020Successful memory involves not only remembering over time but also keeping memories distinct. Computational models suggest that pattern separation appears as a highly... (Review)
Review
Successful memory involves not only remembering over time but also keeping memories distinct. Computational models suggest that pattern separation appears as a highly efficient process to discriminate between overlapping memories. Furthermore, lesion studies have shown that the dentate gyrus (DG) participates in pattern separation. However, these manipulations did not allow identifying the neuronal mechanism underlying pattern separation. The development of different neurophotonics techniques, together with other genetic tools, has been useful for the study of the microcircuit involved in this process. It has been shown that less-overlapped information would generate distinct neuronal representations within the granule cells (GCs). However, because glutamatergic or GABAergic cells in the DG are not functionally or structurally homogeneous, identifying the specific role of the different subpopulations remains elusive. Then, understanding pattern separation requires the ability to manipulate a temporal and spatially specific subset of cells in the DG and ideally to analyze DG cells activity in individuals performing a pattern separation dependent behavioral task. Thus, neurophotonics and calcium imaging techniques in conjunction with activity-dependent promoters and high-resolution microscopy appear as important tools for this endeavor. In this work, we review how different neurophotonics techniques have been implemented in the elucidation of a neuronal network that supports pattern separation alone or in combination with traditional techniques. We discuss the limitation of these techniques and how other neurophotonic techniques could be used to complement the advances presented up to this date.
Topics: Animals; Computer Simulation; Dentate Gyrus; GABAergic Neurons; Humans; Memory; Models, Neurological; Molecular Imaging; Nerve Net; Optical Phenomena
PubMed: 32587504
DOI: 10.3389/fncir.2020.00026 -
NeuroImage Apr 2024In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The...
INTRODUCTION
In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI).
METHODS
We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidβ-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study.
RESULTS
A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory.
DISCUSSION
This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy.
CLINICALTRIALS
GOV: ID NCT04992975 (Clinicaltrial.gov 2023).
Topics: Humans; Alzheimer Disease; Male; Magnetic Resonance Imaging; Female; Aged; Dentate Gyrus; Middle Aged; CA1 Region, Hippocampal; Memory Disorders; Adult; Amyloid beta-Peptides
PubMed: 38614372
DOI: 10.1016/j.neuroimage.2024.120607 -
Proceedings of the National Academy of... May 2022Five decades ago, long-term potentiation (LTP) of synaptic transmission was discovered at entorhinal cortex→dentate gyrus (EC→DG) synapses, but the molecular...
Five decades ago, long-term potentiation (LTP) of synaptic transmission was discovered at entorhinal cortex→dentate gyrus (EC→DG) synapses, but the molecular determinants of EC→DG LTP remain largely unknown. Here, we show that the presynaptic neurexin–ligand cerebellin-4 (Cbln4) is highly expressed in the entorhinal cortex and essential for LTP at EC→DG synapses, but dispensable for basal synaptic transmission at these synapses. Cbln4, when bound to cell-surface neurexins, forms transcellular complexes by interacting with postsynaptic DCC (deleted in colorectal cancer) or neogenin-1. DCC and neogenin-1 act as netrin and repulsive guidance molecule-a (RGMa) receptors that mediate axon guidance in the developing brain, but their binding to Cbln4 raised the possibility that they might additionally function in the mature brain as postsynaptic receptors for presynaptic neurexin/Cbln4 complexes, and that as such receptors, DCC or neogenin-1 might mediate EC→DG LTP that depends on Cbln4. Indeed, we observed that neogenin-1, but not DCC, is abundantly expressed in dentate gyrus granule cells, and that postsynaptic neogenin-1 deletions in dentate granule cells blocked EC→DG LTP, but again did not affect basal synaptic transmission similar to the presynaptic Cbln4 deletions. Thus, binding of presynaptic Cbln4 to postsynaptic neogenin-1 renders EC→DG synapses competent for LTP, but is not required for establishing these synapses or for otherwise enabling their function.
Topics: Animals; Dentate Gyrus; Ligands; Long-Term Potentiation; Membrane Proteins; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Netrin Receptors; Protein Precursors; Synapses; Synaptic Transmission
PubMed: 35544694
DOI: 10.1073/pnas.2123421119 -
Cell Reports Jan 2022During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the...
During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal circuit where self-motion ("where") and sensory cue information ("what") are integrated, but it remains unknown how DG neurons encode this information during cognitive map formation. Using two-photon calcium imaging in mice running on a treadmill along with online cue manipulation, we identify robust sensory cue responses in DG granule cells. Cue cell responses are stable, stimulus-specific, and accompanied by inhibition of nearby neurons. This demonstrates the existence of "cue cells" in addition to better characterized "place cells" in the DG. We hypothesize that the DG supports parallel channels of spatial and non-spatial information that contribute distinctly to downstream computations and affect roles of the DG in spatial navigation and episodic memory.
Topics: Animals; Cues; Dentate Gyrus; Mice; Neurons; Spatial Learning; Spatial Navigation
PubMed: 35045280
DOI: 10.1016/j.celrep.2021.110257 -
Proceedings of the National Academy of... Oct 2022High-frequency oscillatory events, termed ripples, represent synchrony of neural activity in the brain. Recent evidence suggests that medial temporal lobe (MTL) ripples...
High-frequency oscillatory events, termed ripples, represent synchrony of neural activity in the brain. Recent evidence suggests that medial temporal lobe (MTL) ripples support memory retrieval. However, it is unclear if ripples signal the reinstatement of episodic memories. Analyzing electrophysiological MTL recordings from 245 neurosurgical participants performing episodic recall tasks, we find that the rate of hippocampal ripples rises just prior to the free recall of recently formed memories. This prerecall ripple effect (PRE) is stronger in the CA1 and CA3/dentate gyrus (CA3/DG) subfields of the hippocampus than the neighboring MTL regions entorhinal and parahippocampal cortex. PRE is also stronger prior to the retrieval of temporally and semantically clustered, as compared with unclustered, recalls, indicating the involvement of ripples in contextual reinstatement, which is a hallmark of episodic memory.
Topics: CA1 Region, Hippocampal; CA3 Region, Hippocampal; Dentate Gyrus; Humans; Magnetic Resonance Imaging; Memory, Episodic; Mental Recall; Temporal Lobe
PubMed: 36161912
DOI: 10.1073/pnas.2201657119 -
Biological Psychiatry. Cognitive... Jan 2021
Topics: Dentate Gyrus; Depression; Genetic Predisposition to Disease; Hippocampus; Humans
PubMed: 33419511
DOI: 10.1016/j.bpsc.2020.10.016 -
Nature Neuroscience Oct 2019The dentate gyrus-CA3 circuit of the hippocampus is continuously modified by the integration of adult-born dentate granule cells (abDGCs). All abDGCs undergo a prolonged... (Review)
Review
The dentate gyrus-CA3 circuit of the hippocampus is continuously modified by the integration of adult-born dentate granule cells (abDGCs). All abDGCs undergo a prolonged period of maturation, during which they exhibit heightened synaptic plasticity and refinement of electrophysiological properties and connectivity. Consistent with theoretical models and the known functions of the dentate gyrus-CA3 circuit, acute or chronic manipulations of abDGCs support a role for abDGCs in the regulation of memory interference. In this Review, we integrate insights from studies that examine the maturation of abDGCs and their integration into the circuit with network mechanisms that support memory discrimination, consolidation and clearance. We propose that adult hippocampal neurogenesis enables the generation of a library of experiences, each registered in mature abDGC physiology and connectivity. Mature abDGCs recruit inhibitory microcircuits to support pattern separation and memory indexing.
Topics: Animals; CA3 Region, Hippocampal; Dentate Gyrus; Hippocampus; Humans; Memory; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 31477897
DOI: 10.1038/s41593-019-0484-2 -
Neuroscience Jul 2023Neurogenesis occurs throughout adulthood within the dentate gyrus, and evidence indicates that these new neurons play a critical role in both spatial and social memory....
Neurogenesis occurs throughout adulthood within the dentate gyrus, and evidence indicates that these new neurons play a critical role in both spatial and social memory. However, a vast majority of past research on adult neurogenesis has involved experiments with captive mice and rats, making the generalizability of results to natural settings questionable. We assessed the connection between adult neurogenesis and memory by measuring the home range size of wild-caught, free-ranging meadow voles (Microtus pennsylvanicus). Adult male voles (n = 18) were captured, fitted with radio collars, and released back into their natural habitat, where each vole's home range was assessed using 40 radio-telemetry fixes over the course of 5 evenings. Voles were then recaptured, and brain tissue was collected. Cellular markers of cell proliferation (pHisH3, Ki67), neurogenesis (DCX), and pyknosis were labeled on histological sections and then quantified using either fluorescent or light microscopy. Voles with larger home ranges had significantly higher pHisH3+ cell densities within the granule cell layer and subgranular zone (GCL + SGZ) of the dentate gyrus and higher Ki67+ cell densities in the dorsal GCL + SGZ. Voles with larger ranges also had significantly higher pyknotic cell densities in the entire GCL + SGZ and in the dorsal GCL + SGZ. These results support the hypothesis that cell proliferation and cell death within the hippocampus are involved with spatial memory formation. However, a marker of neurogenesis (DCX+) was not correlated with range size, suggesting that there may be selective cellular turnover in the dentate gyrus when a vole is ranging through its environment.
Topics: Animals; Male; Rats; Mice; Dentate Gyrus; Homing Behavior; Ki-67 Antigen; Cell Proliferation; Cell Death; Neurogenesis; Arvicolinae
PubMed: 37245693
DOI: 10.1016/j.neuroscience.2023.05.018 -
The Journal of Physiological Sciences :... May 2024Experiments measuring evoked potentials require flexible and rapid adjustment of stimulation and recording parameters. In this study, we have developed a recording...
Experiments measuring evoked potentials require flexible and rapid adjustment of stimulation and recording parameters. In this study, we have developed a recording system and an associated Android application that allow making such adjustments wirelessly. The system consists of 3 units: for stimulation, recording and control. Most of the modules in this system are custom made, although the stimulator and tablet are off-the-shelf products. When installed on the tablet, our Android application allows wireless communication with the control unit from a distance of 5 m. In testing, the recording unit had low internal noise and displayed signals faithfully. Upon receiving commands from the control unit, the stimulation unit produced precisely timed pulse outputs. Using this system, we were able to record evoked field potentials in the dentate gyrus of a rat; responses increased as expected with increasing stimulation pulse amplitude and duration.
Topics: Animals; Wireless Technology; Rats; Evoked Potentials; Male; Electric Stimulation; Dentate Gyrus
PubMed: 38773373
DOI: 10.1186/s12576-024-00923-6