Advisor(s)
Lynn Dobrunz
Elizabeth Lucas
Committee Member(s)
James Hardaway
Linda Wadiche
Lori McMahon
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Neurobiology
Date of Award
9-11-2025
Abstract
Neuropeptide Y (NPY) serves as a critical endogenous anxiolytic and stress-buffering molecule, yet the temporal and spatial dynamics of NPY+ cells during fear learning re-main unknown. Temporal dynamics can be measured with in vivo calcium imaging tech-niques, which enable real-time monitoring of cell-type-specific neural activity in freely behaving animals. Snapshots of neuronal activation can be measured using c-Fos im-munohistochemistry, thereby providing excellent spatial resolution. Here, I employ cut-ting-edge approaches to characterize the temporal and spatial activation patterns of NPY+ cells in amygdala, a key fear-regulating brain region negatively impacted by aversive events. I first used in vivo fiber photometry, together with the genetically-encoded calci-um sensor GCaMP8f expressed in NPY+ cells, to investigate the temporal resolution of NPY+ cell activation in the amygdala. I showed that footshock causes a robust and re-peatable elevation of calcium in amygdala NPY+ cells in male and female mice, demon-strating that aversive stimulation reliably activates these cells. Consistent with this, amyg-dala NPY+ cells are activated by footshocks during cued fear conditioning. However, amygdala NPY+ cells are not activated in retrieval, or extinction phases of cued fear con-ditioning, indicating that NPY+ cells in other brain regions are likely to be responsible for NPY’s effects on these behaviors. Next, I quantified the distribution of NPY+ cells in different nuclei of the amygdala as well as in hippocampal CA1, a region important for learning and memory. In tandem, I used c-Fos immunohistochemistry to measure the spa-tial patterns of NPY+ neuron activation in amygdala and hippocampus in response to an aversive stimulus. I discovered that NPY+ cells are activated by context and footshock in a sub-region specific manner. By establishing the temporal and spatial patterns of anxio-lytic NPY+ neuron activation, I have advanced our basic biology understanding of how this critical anxiolytic, neuromodulatory system contributes to fear learning. Determining when NPY+ neurons are recruited during distinct phases of fear learning can lead to a more complete picture of the underlying fear circuitry and in turn, aid in the development of new therapeutic tools.
ProQuest ID
Recommended Citation
Perez, Patric, "Amygdala Npy+ Interneurons Are Activated By Aversive Stim-Uli" (2025). All ETDs from UAB. 7397.
https://digitalcommons.library.uab.edu/etd-collection/7397
