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Record W4388592755 · doi:10.1101/2023.11.08.566107

Entorhinal cortex glutamatergic and GABAergic projections bidirectionally control discrimination and generalization of hippocampal representations

2023· preprint· en· W4388592755 on OpenAlexfundno aff
Vincent Robert, Keelin O’Neil, Shannon K. Rashid, Cara D. Johnson, Rodrigo G. De La Torre, Boris V. Zemelman, Claudia Clopath, Jayeeta Basu

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldNeuroscience
TopicMemory and Neural Mechanisms
Canadian institutionsnot available
FundersNational Institutes of HealthYork UniversityJohns Hopkins UniversityLeon Levy FoundationNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthDirectorate for Biological SciencesEpilepsy SocietyMcKnight FoundationAlzheimer's Association
KeywordsGlutamatergicEntorhinal cortexNeuroscienceGABAergicHippocampal formationGeneralizationHippocampusBiologyPsychologyMathematicsGlutamate receptorReceptor

Abstract

fetched live from OpenAlex

Abstract Discrimination and generalization are crucial brain-wide functions for memory and object recognition that utilize pattern separation and completion computations. Circuit mechanisms supporting these operations remain enigmatic. We show lateral entorhinal cortex glutamatergic (LEC GLU ) and GABAergic (LEC GABA ) projections are essential for object recognition memory. Silencing LEC GLU during in vivo two-photon imaging increased the population of active CA3 pyramidal cells but decreased activity rates, suggesting a sparse coding function through local inhibition. Silencing LEC GLU also decreased place cell remapping between different environments validating this circuit drives pattern separation and context discrimination. Optogenetic circuit mapping confirmed that LEC GLU drives dominant feedforward inhibition to prevent CA3 somatic and dendritic spikes. However, conjunctively active LEC GABA suppresses this local inhibition to disinhibit CA3 pyramidal neuron soma and selectively boost integrative output of LEC and CA3 recurrent network. LEC GABA thus promotes pattern completion and context generalization. Indeed, without this disinhibitory input, CA3 place maps show decreased similarity between contexts. Our findings provide circuit mechanisms whereby long-range glutamatergic and GABAergic cortico-hippocampal inputs bidirectionally modulate pattern separation and completion, providing neuronal representations with a dynamic range for context discrimination and generalization.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.052
GPT teacher head0.283
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2023
Admission routes1
Has abstractyes

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