Prenatal exposure to valproic acid enhances synaptic plasticity in the medial prefrontal cortex and fear memories

Brain Res Bull. 2012 Apr 10;87(6):556-63. doi: 10.1016/j.brainresbull.2012.01.011. Epub 2012 Feb 6.

Abstract

The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher brain functions related to cognition, language, sociability and emotion. Hyper-connectivity and hyper-plasticity at the level of the neuronal microcircuit in the medial prefrontal cortex (mPFC) in the valproic acid (VPA) animal model of autism has been suggested. However, the possible alterations at the system levels are not well understood. The present study investigated the basal synaptic transmission and synaptic plasticity in the mPFC in vivo in the VPA rat model of autism. Furthermore, short-term and long-term retention of fear memories were also examined. The findings displayed that paired-pulse facilitation (PPF) and long-term potentiation (LTP), representing short- and long-term synaptic plasticity, were enhanced by the prenatal exposure to VPA. In addition, the short- and long-term fear memories were enhanced. These results suggest that enhanced synaptic plasticity in the mPFC and fear memories might be one of the mechanisms underlying some symptoms of autism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biophysics
  • Conditioning, Psychological / drug effects
  • Disease Models, Animal
  • Electric Stimulation
  • Enzyme Inhibitors / adverse effects*
  • Excitatory Postsynaptic Potentials / drug effects
  • Fear / drug effects*
  • Female
  • Prefrontal Cortex / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Retention, Psychology / drug effects*
  • Synaptic Transmission / drug effects*
  • Time Factors
  • Valproic Acid / adverse effects*

Substances

  • Enzyme Inhibitors
  • Valproic Acid