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The Ipn Regulates Anxiety Independently of Drug Addiction University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2019 The Ipn Regulates Anxiety Independently Of Drug Addiction Ian Alexander Mclaughlin University of Pennsylvania Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Neuroscience and Neurobiology Commons Recommended Citation Mclaughlin, Ian Alexander, "The Ipn Regulates Anxiety Independently Of Drug Addiction" (2019). Publicly Accessible Penn Dissertations. 3600. https://repository.upenn.edu/edissertations/3600 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3600 For more information, please contact [email protected]. The Ipn Regulates Anxiety Independently Of Drug Addiction 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. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Neuroscience First Advisor Mariella . De Biasi Keywords addiction, anxiety, interpeduncular, serotonin Subject Categories Neuroscience and Neurobiology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/3600 THE IPN REGULATES ANXIETY INDEPENDENTLY OF DRUG ADDICTION Ian McLaughlin A DISSERTATION in Neuroscience Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2019 Supervisor of Dissertation _________________________ Mariella De Biasi, PhD Associate Professor of Neuroscience in Psychiatry Graduate Group Chairperson _________________________ Joshua I. Gold, PhD. Professor of Neuroscience Dissertation Committee: Seema Bhatnagar, PhD. Associate Professor of Anesthesiology & Critical Care Julie Blendy, PhD. Professor of Pharmacology Irwin Lucki, PhD. Emeritus Professor of Psychology in Psychiatry Rebecca Ashare, PhD, Assistant Professor of Psychology in Psychiatry THE INTERPEDUNCULAR NUCLEUS REGULATES ANXIETY INDEPENDENTLY OF DRUG ADDICTION COPYRIGHT 2019 Ian Alexander McLaughlin This work is licensed under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 License To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/3.0/us/ Dedication page This work is devoted to my parents, without whom I’d never have developed the curiosity to sustain the stamina necessary to keep pushing the following boulder up this hill. To my wife, Bo, whose enthusiasm, brilliance, ambition, humor, and patience have been an example to which I aspire. And to my daughter, Milü, of whom I’ve been dreaming since before I started this work, and whose smiles kept me sane while writing about it. .,,,***************/,,,,,.... ..../#*,,,,,,*******,,,,,,/((#(#######################################(((((( ,*************/***//,***,.. .......... ..,,,,***********************,,,,,*(#########################(((((((((((( ******//////////*///***,,.......... .... ..,,****////////////////****///**,,,****//(/*,,,,,,,,,,,,******/((((((((( ***//*/////////////(*,.,........ ..,,, ...,,***///////////////((//**/((##(#(*****///((((//*******************////// //**/////////*,. ....... .. .,******//////////((((((((((/*//#%#%%##%%#**///((((#((///**********///////////( //////(/. .....,,,,,.. ,*////////(((((((((((((((((((///#%#////(#%&(////((##(((/////******////////////// #(((*. .............. .....,,*((((((//((((((#((((((((((((#(//(%#(#((((##&(///(((##((((////*//*//////////////// /,. 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