Date of Award

Fall 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

Kwan, Alex

Abstract

Psychedelics are compounds that can alter perception and cognition and are being explored as treatments for depression, anxiety, and substance-use disorders. Yet, the mechanisms by which they reshape brain function remain poorly understood. This dissertation presents four studies in rodent models examining how psychedelics act across synapses, microcircuits, and whole-brain networks. Chapter 1 shows that a single dose of psilocybin promotes plasticity in the frontal cortex. Chapter 2 maps brain-wide activity induced by psilocybin and ketamine, linking shared and distinct effects to gene expression. Chapter 3 extends this approach to multiple psychiatric drugs, using machine learning to classify drug-specific circuit signatures. Chapter 4 examines psilocybin's cell-type-specific effects, revealing interneuron modulation via 5-HT1A receptors with behavioral relevance. Together, these studies provide key multi-scale insight into psychedelic neurobiology and inform development their potential usage for psychiatric treatment.

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