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Scholarly Works (3 results)

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UC Irvine Electronic Theses and Dissertations (2024)

Mental illnesses like substance use and depression impact large portions of the population. Despite extensive research efforts, effective therapeutics for both substance use disorders and depression remain elusive. To fully address this crisis, we need to understand the complex nature of these disorders, which often involve networks that span the entire brain. This complexity underscores the importance of using comprehensive whole-brain imaging and analysis techniques in tandem with functional behavioral assays to develop therapeutic interventions and ultimately improve treatment outcomes. In the following studies, we investigate the relationship between depression- and drug-induced changes to whole-brain activity and resulting behavior. In the first two studies we identify networks of key structures that contribute to improved outcomes in treatment-resistant depression, and determine that these effects are likely modulated by direct input/output connectivity in identified network hubs. We next investigate how adolescent cannabis exposure impacts future withdrawal behaviors. We find that early life cannabis exposure reduces opioid-induced withdrawal symptoms but increases reinstatement of reward, and identify potential brain regions contributing to these results. In the final study, we demonstrate the ability to identify differentially activated populations during opioid withdrawal and specifically modulate them to improve behavioral outcomes. We apply whole-brain cFos imaging, immunohistochemical analysis, fiber photometry, and viral inhibition to demonstrate our ability to gain genetic access to key regions that go on to be important for opioid induced withdrawal behaviors. Together, these studies demonstrate the utility of employing whole-brain activity-based screens in behavioral studies that involve complex networks. These tools can be applied to a wide variety of questions related to drugs of abuse and neuropsychiatric conditions to identify novel target regions and customize treatment options. Future work applying these techniques could provide a key to developing improved therapeutics for a wide range of disorders.

    Creative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2022)
    Graduate physiology programs strive to provide students with in-depth expertise in a particular academic discipline, often facilitating this process in the form of a departmental seminar course. Within the Department of Physiology and Biophysics at the University of California Irvine (UCI), students are required to attend a seminar course, most often designed as a journal club, each quarter until they are ready to graduate. While this format may work well in departments where research topics are closely related, it has historically been less successful in UCI's Department of Physiology and Biophysics, where wide-ranging interests make for little overlap in foundational knowledge, limiting meaningful engagement with the material or with peers in the class. In this paper, we describe a complementary approach of developing a syllabus around student interests and covering topics that are critical for student success but often omitted from graduate curricula, such as interview skills, grant writing, and scientific communication. Results from our preclass survey motivated this approach to the class, and our retrospective survey demonstrated the substantial differences in student engagement, enthusiasm, and perceived benefits of this course relative to the journal club style course. We hope that the success of our course may serve as an exemplar for strategies to engage students more effectively and provide critical training in diverse skillsets that will help students after graduation.
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2022)
      Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.
        Cover page: An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement
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