?4??-GABAA receptors in dorsal hippocampal CA1 of adolescent female rats traffic to the plasma membrane of dendritic spines following voluntary exercise and contribute to protection of animals from activity-based anorexia through localization at excitatory synapses.
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ABSTRACT: In hippocampal CA1 of adolescent female rodents, ?4??-GABAA receptors (?4??-GABAA Rs) suppress excitability of pyramidal neurons through shunting inhibition at excitatory synapses. This contributes to anxiolysis of stressed animals. Socially isolated adolescent female rats with 8 days of wheel access, the last 4 days of which entail restricted food access, have been shown to exhibit excessive exercise, choosing to run instead of eat (activity-based anorexia [ABA]). Upregulation of ?4??-GABAA Rs in the dorsal hippocampal CA1 (DH), seen among some ABA animals, correlates with suppression of excessive exercise. We used electron microscopic immunocytochemistry to show that exercise alone (EX), but not food restriction alone (FR), also augments ?4??-GABAA R expression at axospinous excitatory synapses of the DH (67%, P?=?0.027), relative to socially isolated controls without exercise or food restriction (CON). Relative to CON, ABA animals' synaptic ?4??-GABAA R elevation was modestly elevated (37%), but this level correlated strongly and negatively with individual differences in ABA vulnerability-i.e., food restriction-evoked hyperactivity (Pearson R?=?-0.902, P?=?0.002) and weight changes (R?=?0.822, P?=?0.012). These correlations were absent from FR and EX brains or ventral hippocampus of ABA brains. Comparison to CON of ?4??-GABAA R location in the DH indicated that ABA induces trafficking of ?4??-GABAA R from reserve pools in spine cytoplasm to excitatory synapses. Pair-housing CON animals reduced cytoplasmic ?4??-GABAA R without reducing synaptic ?4??-GABAA R. Thus, exercise induces trafficking of ?4??-GABAA Rs to excitatory synapses, while individual differences in ABA vulnerability are linked most strongly to trafficking of ?4??-GABAA Rs in the reverse direction-from excitatory synapses to the reserve pool during co-occurring food restriction. © 2017 Wiley Periodicals, Inc.
SUBMITTER: Aoki C
PROVIDER: S-EPMC5563482 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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