ePoster

Learning dynamics in development-defined microcircuits is rooted in inhibitory connectivity

Roman Huszar, Artem Kirsanov, Griffin Henze, Dhananjay Huilgol, Josh Huang, Gyorgy Buzsaki
COSYNE 2025(2025)
Montreal, Canada

Conference

COSYNE 2025

Montreal, Canada

Resources

Authors & Affiliations

Roman Huszar, Artem Kirsanov, Griffin Henze, Dhananjay Huilgol, Josh Huang, Gyorgy Buzsaki

Abstract

The hippocampus is a key player in learning and memory. However, the microcircuit logic that endows the hippocampus with these capabilities remains virtually unknown. Hippocampal neurons exhibit tremendous diversity in terms of their gene expression, connectivity, and intrinsic properties. Recent work suggests that this diversity is rooted in the temporal progression of embryonic development, with neurons born at the same gestational timepoint exhibiting shared input and output connectivity, as well as correlated activity in-vivo. In this work, we combined embryonic birthdating of CA3-CA1 neurons and high-density in-vivo electrophysiology with a place-reward association task to study how the encoding of new information is supported by activity within development-defined microcircuits. Same birthdate neurons consistently exhibited highly correlated activity, consistent with their well-known interregional connectivity. By combining contrastive dimensionality reduction with a model explainability approach, we found that components of same birthdate correlations that were later reactivated in offline brain states contributed to the learned encoding of rewards in the population. This effect held for same birthdate microcircuits within CA1 and spanning the CA3-CA1 axis, but not within the CA3 itself, despite higher correlations within these microcircuits in all hippocampal subregions. These distinctions were rooted in regional differences in connectivity between same birthdate pyramidal cells and inhibitory interneurons, which allowed us to observe the reported effects in larger populations by using connectivity as a proxy. Our results suggest that same birthdate circuits spanning the CA3-CA1 axis support the encoding of newly learned content. We speculate that this encoding involves inhibitory plasticity in the CA3-CA1 subcircuits but depends on activity in the CA3 itself. Overall, our results suggest that development-defined microcircuits rooted in inhibitory connectivity constitute preconfigured modules that support the encoding of new memories in the hippocampus.

Unique ID: cosyne-25/learning-dynamics-development-defined-a7bab0e4