Dissertations, Theses, and Capstone Projects

Date of Degree

2-2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Psychology

Advisor

Peter Serrano

Committee Members

Ekaterina Likhtik

Asohan Amarasingham

Subject Categories

Behavioral Neurobiology | Cellular and Molecular Physiology | Computational Neuroscience | Systems Neuroscience

Keywords

Memory, Optogenetics, Electrophysiology, Systems

Abstract

Memories are thought to be encoded by ensembles of neurons called "engram cells", because their artificial activation with optogenetics leads to the behavioral expression of a memory. However, the physiological mechanisms that mediate this process remain unknown. In this thesis, I investigate how optogenetic stimulation of memory-tagged cells changes neuronal firing, spatial coding, and the geometry of neural manifolds. I used an active place avoidance task and a foraging task to label engram cells in the dorsal hippocampus with Channelrhodopsin2 (ChR2). I then recorded the hippocampal activity response to optogenetic stimulation in mice under anesthesia, head-fixed, or freely moving. I found that optogenetic stimulation of memory-tagged cells increased firing rates not only in tagged neurons but also in non-tagged cells. Spatial tuning in CA1 was mostly unperturbed by optogenetic stimulation. Trajectories of neural activity within low-dimensional neural manifolds revealed that stimulation perturbed the system without generating novel trajectories; instead, activity remained embedded within the geometry of endogenous patterns, consistent with the constraints of the hippocampal network. Finally, stimulation alone was sufficient to elicit the behavioral expression of the active place avoidance memory in a neutral, unconditioned arena.

Together, these findings suggest that memory recall is not the result of reactivating a static engram but rather emerges from a dynamic reconfiguration of network activity initiated by tagged ensemble activation. This work challenges the notion of the engram as a localized memory trace and highlights the importance of understanding memory as a distributed and state-dependent process.

This work is embargoed and will be available for download on Saturday, August 01, 2026

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