Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development

Biol Psychiatry. 2006 Dec 1;60(11):1259-67. doi: 10.1016/j.biopsych.2006.05.046. Epub 2006 Sep 1.


Background: Psychiatric disorders such as schizophrenia are believed to emerge from an interaction of several factors. Thus, a genetic predisposition can lead to developmental compromises that may leave the system more susceptible to deficits induced by subsequent environmental variables such as stress.

Methods: The impact of neurodevelopmental interruption induced by exposure of rats prenatally to a compound methylazoxymethanol acetate (MAM) that disrupts neuronal proliferation was investigated using in vivo electrophysiologic recordings from the prefrontal cortex of adult rats.

Results: Prenatal exposure to MAM resulted in alterations in the medial prefrontal cortex indicative of a compromise in information processing. Specifically, we observed a disruption in activity patterns consistent with deficits in neuronal synchronization and abnormal augmentation of synaptic plasticity that was more severely disrupted by stress exposure than in normal animals. Furthermore, these deficits could be reversed by manipulating the mesocortical dopamine system.

Conclusions: These results suggest that disruption of early cortical development causes impairments in medial prefrontal cortical function at adulthood that are more vulnerable to disruptive influences, despite the presence of only subtle structural alterations in the brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Age Factors
  • Animals
  • Animals, Newborn
  • Cell Proliferation* / drug effects
  • Dopamine / pharmacology
  • Electric Stimulation / methods
  • Electroencephalography / drug effects
  • Female
  • Hippocampus / drug effects
  • Male
  • Methylazoxymethanol Acetate / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neuronal Plasticity / radiation effects
  • Neurotoxins / pharmacology
  • Prefrontal Cortex / pathology*
  • Prefrontal Cortex / physiopathology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology*
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Inbred F344
  • Time Factors


  • Neurotoxins
  • Methylazoxymethanol Acetate
  • Dopamine