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Learning Dependent Feedback Regulations of Behavioral Timescale Synaptic Plasticity
Dissertation

Learning Dependent Feedback Regulations of Behavioral Timescale Synaptic Plasticity

Lisandro Martin
Doctor of Philosophy (PhD), Brandeis University, Graduate School of Arts & Sciences
2026
DOI:
https://doi.org/10.48617/etd.1589

Abstract

Behavioral Time Scale Plasticity Feedback Inhibition Interneurons Learning and Memory Place Cells Plasticity Psychology
One of the large, overarching questions in neuroscience is how learning is manifested in the brain. The prevailing theory is that synaptic connections between neurons adapt their strength in response to behavioral experiences. A recently discovered form of synaptic plasticity, behavioral timescale synaptic plasticity (BTSP), has been shown to form place fields in CA1 pyramidal cells of the hippocampus through a single dendritic plateau that potentiates synapses active seconds ago. Previous studies indicate that BTSP is driven by a target signal originating from entorhinal cortex layer 3 (EC3), but this drive diminishes late in learning as CA1 activity increases. This led to the hypothesis that dendritic plateau potentials are a cell-specific error signal induced by a mismatch between CA1 and EC3 activity. We hypothesize that feedback inhibition contributes to error computation by signaling the activity of the CA1 population to the distal tuft and decreasing plateau probability when CA1 activity matches EC3 input. In this thesis, I will present results indicating that oriens lacunosum moleculare (OLM) cells regulate BTSP during learning through feedback inhibition. Our results demonstrate that OLM cell activity adapts to match CA1 activity throughout learning, and that manipulating OLM cells alters the probability of plateau initiation and place field formation.
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Embargoed Access, Embargo ends: 11/19/2026

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