Date of Award

8-2026

Embargo Period

8-8-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

James Otis

Abstract

Post-traumatic stress disorder (PTSD) is characterized by hyperarousal and heightened reactivity that generalize beyond the original traumatic event, yet the neural mechanisms by which prior stress experience biases future fear learning remain poorly understood. Stress-enhanced fear learning (SEFL) is a well-validated rodent model of this phenomenon, in which a severe stressor produces persistent sensitization of subsequent fear acquisition. This dissertation used a 30-day SEFL paradigm to identify the brain-wide functional signature of stress sensitization and to identify candidate neural substrates.

Whole-brain cFos mapping during acute fear acquisition revealed a predominant pattern of suppressed neural activity in sensitized animals, with limbic thalamic nuclei emerging as the most consistently and selectively affected structures. Specifically, cFos expression in the paraventricular nucleus of the thalamus (PVT) positively correlated with individual behavioral sensitization. Chemogenetic inhibition of the PVT confirmed that this correlation reflected a causal role: PVT activity was required for the acquisition of sensitized fear but was dispensable for its later expression, establishing a double dissociation between encoding and retrieval. Together, these findings identify the PVT as a history-dependent gain-control node that selectively amplifies fear encoding in previously stressed animals, and provide the first comprehensive whole-brain functional map of remote stress sensitization.

Rights

Copyright is held by the author, Michael Martino. All rights reserved.

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