ArticleNature medicine2018
Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 185 citations in OpenAlex.
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- ICER-Controlled inhibitory plasticity of amygdala engram neurons regulates fear memory precision.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Suppressing neural stem cell PLA2G7 restores inhibitory circuit function and improves cognition in aging mice.Nature aging · 2026Article
- Article
- Hippocampal CA3 connectomics reveals a gradient of mossy fiber inputs and selective feedforward inhibition onto pyramidal cells.Nature neuroscience · 2026Article
- Neural mechanisms of fear memory precision and generalization: from auditory cortex to amygdala.Translational psychiatry · 2026Review
- The role of GABANeuroscience and biobehavioral reviews · 2026Review
- Article
- Aberrant dopaminergic activity during consolidation causes age-related memory generalization in Drosophila.PLoS biology · 2026Article
- Role of the hippocampus in systems consolidation of remote fear memory.Experimental & molecular medicine · 2026Review
- Dentate Gyrus Engrams in Fear and Reward: Mechanistic Principles, Critical Gaps, and Paths to Translation.Journal of neurochemistry · 2026Review
- Engram Synapses and Synapse Dynamics in Memory Processing.Journal of neurochemistry · 2026Review
- Diverse and location-specific roles of PlexinA2, PlexinA4, and NCAM in developing hippocampal mossy fibers.Translational psychiatry · 2026Article
- Distinct CA1 inputs support shifts in neural dimensionality and memory resolution.bioRxiv : the preprint server for biology · 2026Article
- Tuning excitatory input to fast-spiking parvalbumin-positive interneurons: a lever for plasticity and hyperexcitability across the lifespan.Frontiers in synaptic neuroscience · 2026Article
- Functional loss of PKMζ in the dorsal hippocampus potentiates the time-dependent increase in false contextual fear memory and impairs spatial recognition memory in mice.Frontiers in behavioral neuroscience · 2026Article
- Modulating NLRP3 Inflammasome Activity and Enhancing Cortical Synaptic Plasticity: Nanoparticulate Hydrogen's Role in Relief of Post-traumatic Anxiety-like Behaviors in Rats.Molecular neurobiology · 2025Article
- A dynamic gene regulatory code drives synaptic development of hippocampal granule cells.Science advances · 2025Article
- Inhibitory Neurons Marked by the Connectivity Molecule Kirrel3 Regulate Memory Precision.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Noncanonical circuits, states, and computations of the hippocampus.Science (New York, N.Y.) · 2025Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Memories become less precise and generalized over time as memory traces reorganize in hippocampal-cortical networks. Increased time-dependent loss of memory precision is characterized by an overgeneralization of fear in individuals with post-traumatic stress disorder (PTSD) or age-related cognitive impairments. In the hippocampal dentate gyrus (DG), memories are thought to be encoded by so-called 'engram-bearing' dentate granule cells (eDGCs). Here we show, using rodents, that contextual fear conditioning increases connectivity between eDGCs and inhibitory interneurons (INs) in the downstream hippocampal CA3 region. We identify actin-binding LIM protein 3 (ABLIM3) as a mossy-fiber-terminal-localized cytoskeletal factor whose levels decrease after learning. Downregulation of ABLIM3 expression in DGCs was sufficient to increase connectivity with CA3 stratum lucidum INs (SLINs), promote parvalbumin (PV)-expressing SLIN activation, enhance feedforward inhibition onto CA3 and maintain a fear memory engram in the DG over time. Furthermore, downregulation of ABLIM3 expression in DGCs conferred conditioned context-specific reactivation of memory traces in hippocampal-cortical and amygdalar networks and decreased fear memory generalization at remote (i.e., distal) time points. Consistent with the observation of age-related hyperactivity of CA3, learning failed to increase DGC-SLIN connectivity in 17-month-old mice, whereas downregulation of ABLIM3 expression was sufficient to restore DGC-SLIN connectivity, increase PV+ SLIN activation and improve the precision of remote memories. These studies exemplify a connectivity-based strategy that targets a molecular brake of feedforward inhibition in DG-CA3 and may be harnessed to decrease time-dependent memory generalization in individuals with PTSD and improve memory precision in aging individuals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.