Author

Nguyen Vu

Date of Award

Spring 2019

Document Type

Open Access Thesis

Department

Biomedical Science

First Advisor

David D. Mott

Abstract

Emotion is a crucial component of the decision-making process. The amygdala, known as the “orchestrator” of the emotion circuit, associates emotional valence with incoming sensory stimuli and thus contributes to decision- making. Within the basolateral nucleus of the amygdala (BLA), spatially segregated and genetically distinct pyramidal neurons (PNs) have been identified based on their correspondence to distinct behavioral stimuli. These PNs project to several brain regions mediating different aspects of the emotional spectrum.

For example, BLA PNs projecting to prelimbic (PL) and infralimbic (IL) cortex are involved in fear acquisition and fear extinction, respectively. However, the mechanism by which these distinct PNs are modulated and whether this modulation differs depending on their projection targets remains unclear. The BLA is densely innervated by cholinergic fibers from the basal forebrain, and the contributions of acetylcholine (ACh) to selective attention, emotion, and other cognitive functions suggest a modulatory role of this neurotransmitter in the BLA. Here, we have used confocal immunofluorescence to examine the anatomical distribution of cholinergic markers across the BLA relative to PNs, including those projecting to PL and IL, to establish an anatomical basis for cholinergic modulation of different PNs. Immunoreactivity for both postsynaptic M1 muscarinic receptors and vesicular ACh transporter (vAChT), a marker of cholinergic terminals, was significantly greater in the dorsorostral region of the

anterior BLA (BLAa) compared to other regions of the BLA or other amygdalar subnuclei (n=6). M1R immunoreactivity was preferentially localized to magnocellular PNs in the BLAa (n = 6). These magnocellular PNs have previously been found to be responsive to stimuli of negative valence. In contrast, parvocellular PNs, which are responsive to stimuli of positive valence, were located in posterior BLA (BLAp), exhibited significantly less M1R immunoreactivity and were associated with significantly less cholinergic innervation. PNs projecting to PL (PL-projectors), which were prominently found in BLAa, expressed higher M1 intensity than those projecting to IL, which were more equally distributed between BLA subnuclei. Altogether, these data provide an anatomical basis for preferential cholinergic modulation of negative valence- encoding PNs in the BLA.

Available for download on Monday, May 11, 2020

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