Date of Award

Fall 2019

Document Type

Open Access Dissertation

Department

Exercise Science

First Advisor

David D. Mott

Abstract

The basolateral amygdala (BL) is critical for emotional memory acquisition and expression. It receives afferent projections from both cortical and subcortical regions that send glutamatergic transmission to the BL. This input conveys information necessary for survival, including information about one’s behavioral state and environment. How this information is integrated and processed by the BL, however, remains largely unknown. Interestingly, the BL receives the densest amount of cholinergic innervation from the basal forebrain. This acetylcholine (ACh) can modulate emotional memories, but how it modulates specific afferent inputs to the BL is unexplored. To answer this question, we used brain slice field and whole cell electrophysiology, optogenetics, and pharmacological tools to investigate how released endogenous ACh modulates afferent input to the BL. We found that endogenous ACh suppresses cortical input to the BL through muscarinic receptors. We then further explored this modulation by optogenetically activating prelimbic (PL) and thalamic (THAL) input to the BL and pharmacologically activating muscarinic ACh receptors to examine pathway-specific regulation of glutamatergic transmission from these inputs. Muscarine, by acting on M3 and M4 receptors at PL synapses and M3 receptors at THAL synapses, suppressed glutamatergic input from both regions. However, muscarinic receptor activation inhibited the prelimbic input to a significantly greater extent than the thalamic. Furthermore, in examining the mechanisms underlying this inhibition, it was found that muscarinic inhibition of these two pathways occurs through distinct mechanisms. At PL input muscarinic receptors inhibit

glutamatergic transmission through an endocannabinoid independent mechanisms whereas they inhibit thalamic input through an endocannabinoid-dependent mechanism. Additionally, muscarinic receptors displayed frequency-dependent regulation of glutamate transmission. When the PL and THAL inputs were stimulated at low frequency trains (1Hz), muscarinic inhibition was consistent throughout the train. However, when PL and THAL were stimulated at gamma frequency trains (40Hz), muscarinic inhibition remained intact throughout the train at THAL inputs, but was relieved at PL inputs. Taken together, these findings suggest differential modulatory mechanisms during enhanced cholinergic tone in the BL, such as during exercise or unexpected stimuli. However, this inhibition is frequency dependent. During behavioral states in which the PL is oscillating at gamma frequency, that muscarinic inhibition could be overcome. Together, these results indicate unique modulatory mechanisms conferred upon the PL and THAL input to the BL and could serve as rich avenues for pharmaceutical manipulations in future behavioral studies.

Available for download on Wednesday, December 16, 2020

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