The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model

PLoS One. 2013;8(1):e55248. doi: 10.1371/journal.pone.0055248. Epub 2013 Jan 29.

Abstract

The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28-35 days valproate (VPA)-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA) of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP) while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF) at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC) frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I) balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiopathology*
  • Analysis of Variance
  • Animals
  • Autistic Disorder / chemically induced
  • Autistic Disorder / metabolism*
  • Conditioning, Operant
  • Excitatory Postsynaptic Potentials / physiology*
  • Fear / physiology
  • Histological Techniques
  • Inhibitory Postsynaptic Potentials / physiology*
  • Long-Term Potentiation / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Social Behavior
  • Synapses / physiology*
  • Valproic Acid / toxicity*

Substances

  • Valproic Acid

Grant support

Funding provided by the National Science Council, Taiwan (http://web1.nsc.gov.tw/mp.aspx?mp=7; NSC 99-2628-B-006-013, NSC 96-2314-B-006-056, NSC 100-2320-B-010-033-MY2); Aim for the Top University Plan from the National Cheng Kung University (http://top-en.ncku.edu.tw/bin/home.php); Aim for the Top University Plan from the National Yang-Ming University (http://www.ym.edu.tw/top/eng/index.html); and National Cheng Kung Hospital (http://www.hosp.ncku.edu.tw/nckm/english/HomeStyle.aspx?Type=11&ContentPage=0; NCKUH-10005008). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.