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Excitatory synapses on dendritic shafts of the caudal basal amygdala exhibit elevated levels of GABA sub(A) receptor [alpha]4 subunits following the induction of activity-based anorexia

Anorexia nervosa (AN) is an eating disorder characterized by self-imposed severe starvation, excessive exercise, and anxiety. The onset of AN is most often at puberty, suggesting that gonadal hormonal fluctuations may contribute to AN vulnerability. Activity-based anorexia (ABA) is an animal model t...

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Published in:Synapse (New York, N.Y.) N.Y.), 2014-01, Vol.68 (1), p.1-15
Main Authors: Wable, Gauri S, Barbarich-Marsteller, Nicole C, Chowdhury, Tara G, Sabaliauskas, Nicole A, Farb, Claudia R, Aoki, Chiye
Format: Article
Language:English
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Summary:Anorexia nervosa (AN) is an eating disorder characterized by self-imposed severe starvation, excessive exercise, and anxiety. The onset of AN is most often at puberty, suggesting that gonadal hormonal fluctuations may contribute to AN vulnerability. Activity-based anorexia (ABA) is an animal model that reproduces some of the behavioral phenotypes of AN, including the paradoxical increase in voluntary exercise following food restriction. The basal amygdala as well as the GABAergic system regulate trait anxiety. We therefore examined the subcellular distribution of GABA receptors (GABARs) in the basal amygdala of female pubertal rats and specifically of their [alpha]4 subunits, because expression of [alpha]4-containing GABARs is regulated by gonadal hormone fluctuations. Moreover, because these GABARs reduce neuronal excitability through shunting of EPSPs, we quantified the frequency of occurrence of these GABARs adjacent to excitatory synapses. Electron microscopic immunoctychemistry revealed no change in the frequency of association of [alpha]4 subunits with excitatory synapses on dendritic spines, whether in the anterior (Bregma -2.8 mm) or caudal (Bregma -3.8 mm) portion of the basal amygdala. Sholl analysis of golgi-stained neurons also revealed no change in the extent of dendritic branching by these densely spiny, pyramidal-like neurons. However, there was an increase of membranous [alpha]4 subunits near excitatory synapses on dendritic shafts, specifically in the caudal basal amygdala, and this was accompanied by a rise of [alpha]4 subunits intracellularly. Because most dendritic shafts exhibiting excitatory synapses are GABAergic interneurons, the results predict disinhibition, which would increase excitability of the amygdaloid network, in turn augmenting ABA animals' anxiety. Synapse, 68:1-15, 2014. [copy 2013 Wiley Periodicals, Inc.
ISSN:0887-4476
1098-2396
DOI:10.1002/syn.21690