Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Mariella . De Biasi

Abstract

ABSTRACT

THE INTERPEDUNCULAR NUCLEUS REGULATES ANXIETY

Ian A. McLaughlin

Dr. Mariella De Biasi

This work is devoted to better understanding how a component of one of the principle anatomical intersections of cognitive, emotional, and motivational signaling regulates anxiety and addiction. The majority of my work focused on the interpeduncular nucleus (IPN). The IPN and its principle source of afferent signals, the medial habenula (MHb), comprise a junction of signaling within the diencephalic conduction system (DDC). Along with the medial forebrain bundle, the DDC is a highly conserved pathway by which signals from the limbic forebrain reach the midbrain and hindbrain. Work in our lab and others has implicated the MHb-IPN axis in the aversive affective and somatic withdrawal syndrome that manifests following cessation of chronic exposure to habit-forming drugs, including alcohol, nicotine, and opioids. Given that functional role, I sought to establish if this pathway regulates affect independently of chronic drug exposure.

In addition to my primary work, additional experiments I performed contributed to the growing understanding of how this pathway functions within the context of addiction. In particular, I contributed to studies focused on how the presence of the α5 nicotinic acetylcholine receptor subunit (nAChRs) in the IPN and its neighboring structure, the ventral tegmental area (VTA), influences predispositions to alcohol and nicotine addictions in animal models.

Using in vivo chemogenetics, viral tracing and receptor subunit rescue, microdialysis, and behavioral analyses, I worked to evaluate how perturbations of signaling within the IPN or VTA affected mouse behavior.

Overall, I have found that the IPN does indeed regulate affect independently of chronic drug exposure, and that signaling via the α5 nAChR subunit within both the IPN and VTA significantly regulates drug-taking behavior.

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