α4βδ-GABA A 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

Chiye Aoki, Yi Wen Chen, Tara Gunkali Chowdhury, Walter Piper

Research output: Contribution to journalArticle

Abstract

In hippocampal CA1 of adolescent female rodents, α4βδ-GABAA receptors (α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-GABAA R location in the DH indicated that ABA induces trafficking of α4βδ-GABAA R from reserve pools in spine cytoplasm to excitatory synapses. Pair-housing CON animals reduced cytoplasmic α4βδ-GABAA R without reducing synaptic α4βδ-GABAA R. Thus, exercise induces trafficking of α4βδ-GABAA Rs to excitatory synapses, while individual differences in ABA vulnerability are linked most strongly to trafficking of α4βδ-GABAA Rs in the reverse direction-from excitatory synapses to the reserve pool during co-occurring food restriction.

Original languageEnglish (US)
Pages (from-to)1450-1466
Number of pages17
JournalJournal of neuroscience research
Volume96
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Dendritic Spines
Anorexia
GABA-A Receptors
Synapses
Cell Membrane
Exercise
Food
Individuality
Animal Housing
Pyramidal Cells
Brain
Rodentia
Hippocampus
Cytoplasm
Spine
Up-Regulation
Immunohistochemistry
Electrons
Weights and Measures

Keywords

  • anorexia nervosa
  • anxiolysis
  • dorsal hippocampus
  • electron microscopic immunocytochemistry
  • exercise
  • GABA(A) receptor subunit delta
  • neuromodulation
  • nonsynaptic
  • plasticity
  • receptor trafficking
  • social isolation
  • tonic inhibition
  • ventral hippocampus
  • wheel running

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

@article{2b1a6650a80d4a10b23524bc13495cb7,
title = "α4βδ-GABA A 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",
abstract = "In hippocampal CA1 of adolescent female rodents, α4βδ-GABAA receptors (α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-GABAA R location in the DH indicated that ABA induces trafficking of α4βδ-GABAA R from reserve pools in spine cytoplasm to excitatory synapses. Pair-housing CON animals reduced cytoplasmic α4βδ-GABAA R without reducing synaptic α4βδ-GABAA R. Thus, exercise induces trafficking of α4βδ-GABAA Rs to excitatory synapses, while individual differences in ABA vulnerability are linked most strongly to trafficking of α4βδ-GABAA Rs in the reverse direction-from excitatory synapses to the reserve pool during co-occurring food restriction.",
keywords = "anorexia nervosa, anxiolysis, dorsal hippocampus, electron microscopic immunocytochemistry, exercise, GABA(A) receptor subunit delta, neuromodulation, nonsynaptic, plasticity, receptor trafficking, social isolation, tonic inhibition, ventral hippocampus, wheel running",
author = "Chiye Aoki and Chen, {Yi Wen} and Chowdhury, {Tara Gunkali} and Walter Piper",
year = "2018",
month = "9",
day = "1",
doi = "10.1002/jnr.24035",
language = "English (US)",
volume = "96",
pages = "1450--1466",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
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TY - JOUR

T1 - α4βδ-GABA A 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

AU - Aoki, Chiye

AU - Chen, Yi Wen

AU - Chowdhury, Tara Gunkali

AU - Piper, Walter

PY - 2018/9/1

Y1 - 2018/9/1

N2 - In hippocampal CA1 of adolescent female rodents, α4βδ-GABAA receptors (α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-GABAA R location in the DH indicated that ABA induces trafficking of α4βδ-GABAA R from reserve pools in spine cytoplasm to excitatory synapses. Pair-housing CON animals reduced cytoplasmic α4βδ-GABAA R without reducing synaptic α4βδ-GABAA R. Thus, exercise induces trafficking of α4βδ-GABAA Rs to excitatory synapses, while individual differences in ABA vulnerability are linked most strongly to trafficking of α4βδ-GABAA Rs in the reverse direction-from excitatory synapses to the reserve pool during co-occurring food restriction.

AB - In hippocampal CA1 of adolescent female rodents, α4βδ-GABAA receptors (α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-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 α4βδ-GABAA R location in the DH indicated that ABA induces trafficking of α4βδ-GABAA R from reserve pools in spine cytoplasm to excitatory synapses. Pair-housing CON animals reduced cytoplasmic α4βδ-GABAA R without reducing synaptic α4βδ-GABAA R. Thus, exercise induces trafficking of α4βδ-GABAA Rs to excitatory synapses, while individual differences in ABA vulnerability are linked most strongly to trafficking of α4βδ-GABAA Rs in the reverse direction-from excitatory synapses to the reserve pool during co-occurring food restriction.

KW - anorexia nervosa

KW - anxiolysis

KW - dorsal hippocampus

KW - electron microscopic immunocytochemistry

KW - exercise

KW - GABA(A) receptor subunit delta

KW - neuromodulation

KW - nonsynaptic

KW - plasticity

KW - receptor trafficking

KW - social isolation

KW - tonic inhibition

KW - ventral hippocampus

KW - wheel running

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U2 - 10.1002/jnr.24035

DO - 10.1002/jnr.24035

M3 - Article

C2 - 28218471

AN - SCOPUS:85048390308

VL - 96

SP - 1450

EP - 1466

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 9

ER -