CELL TYPE-SPECIFIC EFFECTS OF OPIOID DEPENDENCE ON CENTRAL AMYGDALA NEURONS

Opioid use disorder and chronic pain impact millions of Americans every year. Given the interactions of pain with opioid withdrawal, it is critical to understand how the neural substrates for pain, such as the central nucleus of the amygdala (CeA), are impacted by opioid dependence. Growing evidence reveals that the CeA comprises multiple functional cell-types. While decades of research implicate the CeA in opioid withdrawal, the cell type-identity of the affected CeA cells has received little attention. In this dissertation, I profile a major subtype of neurons in the central nucleus of the amgydala – CeLCPKCδ neurons, which have a well-supported role in maintaining chronic pain states —in the context of opioid withdrawal. I describe robust hyperactivity of CeLCPKCδ neurons during opioid withdrawal across multiple timescales, and show that chronic suppression of their activity abrogates somatic withdrawal signs during fentanyl abstinence. I then investigate presynaptic sources of hyperactivity from cellular dependence by comparing monosynaptic inputs to CeLCPKCδ neurons and μOR-expressing inputs to the CeA. Finally, using novel tools for genetic targeting of µOR+ neurons, I complement this profiling of CeLCPKCδ neurons by beginning to profile the μOR-expressing population of CeA neurons (CeAμOR). I describe important similarities and differences between these two overlapping populations. Collectively, the results of these studies indicate cell type-specific effects of opioid dependence on withdrawal in the central amygdala, position CeLCPKCδ as a shared neural substrate for the interaction of pain and opioid withdrawal and highlight the importance of brain region- and cell type-specific investigations in the context of neuroscience.

Author dc:creator

• Wooldridge, Lisa

Advisor dc:contributor.advisor

• Corder, Gregory, F.

• Neuroscience and Neurobiology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/61829

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/61829