An Investigation into Orbitofrontal Cortex’s Role in Driving Compulsive-Like Behavior Restricted; Files Only

Abstract

Compulsions involve the preservation of behavior in the face of adverse consequences. In human patients with obsessive compulsive disorder (OCD), the orbitofrontal cortex (OFC) is hyperactive. We have demonstrated in mice bred experimentally to display compulsive-like behavior that chemogenetic inhibition of excitatory neurons in the OFC or a single dose of ketamine can reduce their compulsive-like grooming, suggesting that the OFC drives compulsive-like behavior. Ketamine has been shown to change dendritic spine morphology in the prefrontal cortex and rapidly reduce symptoms of OCD in human patients and compulsive-like behavior in animal models for studying compulsion. In addition to synaptic contacts within the OFC as being a potential mechanism that leads to compulsive-like behavior, evidence suggests that melanocortin 4 receptor (MC4R) could also play a key role. Here we hypothesized that ketamine rescues compulsive-like grooming in experimentally-bred mice through changing dendritic spines, which house the majority of excitatory synapses in the brain, and further, that hyperactive MC4R+ neurons in the OFC drive compulsive-like behavior. Mushroom to thin spine ratios appeared to have a wide dendrite-to-dendrite variance in the experimentally-bred mice that was normalized by ketamine treatment, though further investigation is needed. Meanwhile, chemogenetic stimulation of MC4R+ neurons in the OFC induced compulsive-like grooming. These results serve as stepping stones for our future efforts in investigating ketamine’s anti-compulsive properties mediated via OFC dendritic spines, as well as molecular factors such as MC4R.

Table of Contents

Abstract……………………………………………………………..…………………1

 

Introduction…………………………………..……………………………………......1

 

Methods…………………………………..……………………………………………3

 

Result……………………………………………………………..……………………6

 

Discussion..……………….……………………………………………..………….....9

 

Conclusion...……………………………………………………………..…………...12

 

Bibliography……………………………………………………………..…………...12

 

Supplementary Data………………………………………………….…….....……...14

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Parola chiave	OFC Orbitofrontal Cortex Dendritic Spine Compulsion OCD MC4R Ketamine
Committee Chair / Thesis Advisor	Gourley, Shannon, Emory University
Committee Members	Thompson, Richmond, Emory University Liu, Robert, Emory University

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