Chronic stress enhances synaptic plasticity due to disinhibition in the anterior cingulate cortex and induces hyper-locomotion in mice

Neuropharmacology. Mar-Apr 2010;58(4-5):746-57. doi: 10.1016/j.neuropharm.2009.12.011. Epub 2009 Dec 24.


The anterior cingulate cortex (ACC) is involved in the pathophysiology of a variety of mental disorders, many of which are exacerbated by stress. There are few studies, however, of stress-induced modification of synaptic function in the ACC that is relevant to emotional behavior. We investigated the effects of chronic restraint stress (CRS) on behavior and synaptic function in layers II/III of the ACC in mice. The duration of field excitatory postsynaptic potentials (fEPSPs) was longer in CRS mice than in control mice. The frequency of miniature inhibitory postsynaptic currents (mIPSCs) recorded by whole-cell patch-clamping was reduced in CRS mice, while miniature excitatory postsynaptic currents (mEPSCs) remained unchanged. Paired-pulse ratios (PPRs) of the fEPSP and evoked EPSC were larger in CRS. There was no difference in NMDA component of evoked EPSCs between the groups. Both long-term potentiation (LTP) and long-term depression of fEPSP were larger in CRS mice than in control mice. The differences between the groups in fEPSP duration, PPRs and LTP level were not observed when the GABA(A) receptor was blocked by bicuculline. Compared to control mice, CRS mice exhibited hyper-locomotive activity in an open field test, while no difference was observed between the groups in anxiety-like behavior in a light/dark choice test. CRS mice displayed decreased freezing behavior in fear conditioning tests compared to control mice. These findings suggest that CRS facilitates synaptic plasticity in the ACC via increased excitability due to disinhibition of GABA(A) receptor signalling, which may underlie induction of behavioral hyper-locomotive activity after CRS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / physiology
  • Chronic Disease
  • Excitatory Postsynaptic Potentials / physiology*
  • Gyrus Cinguli / physiology*
  • Hyperkinesis / etiology
  • Hyperkinesis / physiopathology*
  • Hyperkinesis / psychology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / physiology
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology*
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology