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Differential mGluR5 expression in response to the same stress causes individually adapted hippocampal network activity.

 Yeong Shin Yim  ;  Woongsu Han  ;  Jeho Seo  ;  Chul Hoon Kim  ;  Dong Goo Kim 
 Biochemical and Biophysical Research Communications, Vol.495(1) : 1305-1311, 2018 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Action Potentials/physiology* ; Animals ; Electroencephalography/methods ; Gene Expression Regulation/physiology ; Hippocampus/physiology* ; Male ; Nerve Net/physiology* ; Neuronal Plasticity/physiology ; Neurons/physiology* ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5/metabolism* ; Stress, Physiological/physiology* ; Theta Rhythm/physiology*
EEG ; Hippocampus ; Methylation ; Stress ; mGluR5
Individual differences in stress vulnerability and resilience have been observed even within a single cohort of inbred rats or mice. Stress phenotypes are typically quantified as changes in the behavior of experimental animals, which is the outcome of altered electrical activity of the brain network. Although mGluR5 is associated with individual vulnerability to stress and can act as a sensitive biomarker of stress adaptation, our understanding of mGluR5-dependent modifications to neural network activities in vivo remains limited. Here, we examined individual rats for changes in hippocampal mGluR5 expression induced by restraint stress and found that these changes cause accompanying changes in hippocampal electroencephalography (EEG) activity. We found six days of restraint stress caused variable changes in hippocampal mGluR5 expression, ranging from 20.9% to 210.7% of the control group. The low mGluR5 protein group (LE) showed increased methylation of the mGluR5 CpG island, reduced mGluR5 mRNA levels, and unaltered basal EEG theta spectral power between stress day 1 and 6. In contrast, the high mGluR5 protein group (HE) showed reduced methylation of CpG sites, increased mGluR5 mRNA expression, and reduced basal theta spectral power on stress day 6. We also found that injection of lentiviruses expressing mGluR5-specific shRNAs into the hippocampus rescued this reduction in baseline theta power in HE rats. These data suggest a causal relationship between individual differences in the changes in hippocampal mGluR5 expression induced by repetitive restraint stress and the accompanying changes in ensemble neural activity in the hippocampus.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Han, Woong Su(한웅수) ORCID logo https://orcid.org/0000-0002-4250-1124
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