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EXAMINING THE SEX-DEPENDENT EFFECTS OF CHRONIC INTERMITTENT ETHANOL AND WITHDRAWAL ON BASOLATERAL AMYGDALA NEURONS THAT PROJECT TO THE NUCLEUS ACCUMBENS AND BED NUCLEUS OF THE STRIA TERMINALIS

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title
EXAMINING THE SEX-DEPENDENT EFFECTS OF CHRONIC INTERMITTENT ETHANOL AND WITHDRAWAL ON BASOLATERAL AMYGDALA NEURONS THAT PROJECT TO THE NUCLEUS ACCUMBENS AND BED NUCLEUS OF THE STRIA TERMINALIS
author
Price, Michaela
abstract
Alcohol use disorder is a chronic relapsing disorder characterized by excessive alcohol consumption and withdrawal symptoms like anxiety. Withdrawal-induced anxiety is also a strong predictor of relapse. The basolateral amygdala (BLA) is one of several brain regions that regulates alcohol intake and anxiety-like behavior. Extensive literature illustrates that inducing alcohol dependence using the chronic intermittent ethanol and withdrawal (CIE/WD) paradigm produces a pathological shift in the excitatory-inhibitory balance within the BLA towards greater excitation of BLA principal neurons. The following dissertation expands upon these findings by utilizing whole-cell patch-clamp electrophysiology to examine CIE/WD-mediated changes to glutamatergic and GABAergic function within the BLA. Specifically, this dissertation examines neurophysiological changes to BLA principal neuron populations defined by their downstream projections, in particular those that project to the nucleus accumbens core (BLA-NAC neurons) or dorsal bed nucleus of the stria terminalis (BLA-dBNST neurons). These populations were chosen because they regulate alcohol intake and anxiety-like behavior, respectively. BLA principal neurons receive glutamatergic afferents from two distinct input pathways: the ‘lateral’ external capsule and the ‘medial’ stria terminalis. In addition, principal neurons are regulated by populations of GABAergic interneurons, including lateral paracapsular cells (LPCs) and ‘local’ interneurons. In Chapter 2, we demonstrate that CIE/WD increases glutamate release from stria terminalis inputs onto BLA-dBNST neurons in both sexes. CIE/WD also selectively increases postsynaptic glutamatergic function at external capsule synapses with BLA-NAC neurons from male rats and BLA-dBNST neurons from female rats. In Chapter 3, we reveal that CIE/WD reduces GABA release from LPCs onto BLA-NAC neurons from male rats. CIE/WD also decreases presynaptic GABAergic function at ‘local’ interneuron synapses with BLA-dBNST neurons from both sexes. Notably, BLA-NAC neurons from female rats are insensitive to the CIE/WD-mediated effects on glutamatergic and GABAergic signaling. In Chapter 4, behavioral data revealed that chemogenetic inhibition of BLA-dBNST neurons alleviates withdrawal-induced anxiety-like behavior specifically in male rats. As expected, BLA-NAC neurons do not regulate withdrawal-induced anxiety-like behavior in either sex. Collectively, these findings demonstrate that CIE/WD produces input-, projection-, and sex-specific effects on the neurophysiology of BLA principal neurons. Furthermore, these experiments illustrate that BLA-dBNST neurons regulate withdrawal-induced anxiety-like behavior.
subject
anxiety
basolateral amygdala
chronic intermittent ethanol
excitability
GABA
glutamate
contributor
McCool, Brian A (advisor)
Martin, Thomas J (committee member)
Chen, Rong (committee member)
Jones, Sara (committee member)
Gould, Robert (committee member)
date
2024-05-23T08:36:21Z (accessioned)
2024 (issued)
degree
Neuroscience (discipline)
embargo
2024-11-22 (terms)
2024-11-22 (liftdate)
identifier
http://hdl.handle.net/10339/109442 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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