Date of Award

Fall 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdepartmental Neuroscience Program

First Advisor

Kwan, Alex

Abstract

Psychedelics are amid a scientific renaissance driven by their therapeutic promise for mental illnesses. This dissertation examines the neural mechanisms that underlie the acute and long- term actions of psilocybin, a serotonergic psychedelic found in magic mushrooms and an emerging rapid antidepressant. Here we used cutting-edge in vivo techniques to investigate psilocybin's effects in the medial frontal cortex of mice, with a focus on the structure and function of dendrites. Four key findings emerged. First, a single treatment with psilocybin induces persistent dendritic spinogenesis (Chapter 1). The drug-evoked changes in neuronal structure and function varies for subtypes of excitatory pyramidal neurons (Chapter 2), which may also relate to varied effects on subtypes of GABAergic inhibitory interneurons (Chapter 3). Last, psilocybin's acute effects on dendritic activity are modulated by distinct serotonin receptors and arousal states (Chapter 4). These mechanistic insights advance the knowledge of how psychedelics work and their potential to treat depression and other psychiatric disorders.

Download

Share

COinS