Dissertations, Theses, and Capstone Projects

Date of Degree

9-2022

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Jeff Beeler

Committee Members

Leora Yetikoff

Joshua Brumberg

Robert Ranaldi

Saleem Nicola

Subject Categories

Animal Studies | Behavioral Neurobiology | Developmental Neuroscience

Keywords

high fat diet, silent synapses, striatum, addiction

Abstract

Obesity and drugs of abuse share overlapping neural circuits and behaviors. Cravings for drugs of abuse increase during abstinence, a phenomenon known as incubation. In obesity, increased craving is observed in individuals during dieting. Diets often fail, with return to- or increase above- original weight. The extent to which this reflects an incubation phenomenon has not been carefully examined. One mechanism underlying incubation is the reemergence of a developmental mechanism called silent synapses. Silent synapses are 'temporary' synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. Drugs of abuse increase silent synapses during adulthood and may facilitate reorganizing brain circuits around drugs, facilitating addiction and contributing to relapse. Whether highly palatable diets cause circuit reorganization similar to drugs of abuse has not been carefully studied before. Like drugs of abuse, high fat diet increases silent synapse percentages in the direct and indirect pathways in the dorsolateral striatum after six weeks of consumption. Here, we have tested the pathway-specific details by which these silent synapses are formed, such as time course, mechanism, and basal characteristics. We also tested whether there are differences in silent synapses based on afferent pathway input via the M1 cortex or parafascicular nuclei of the thalamus. We have also tested whether chronic consumption of a high-fat diet creates an incubation effect, in which craving for high fat diet is increased after a period of withdrawal via a lever pressing paradigm. Finally, we have examined the changes in spine density and morphology of direct and indirect pathway medium spiny neurons in response to chronic high fat diet consumption.

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