Early cognitive experience prevents adult deficits in a neurodevelopmental schizophrenia model

Neuron. 2012 Aug 23;75(4):714-24. doi: 10.1016/j.neuron.2012.06.016.

Abstract

Brain abnormalities acquired early in life may cause schizophrenia, characterized by adulthood onset of psychosis, affective flattening, and cognitive impairments. Cognitive symptoms, like impaired cognitive control, are now recognized to be important treatment targets but cognition-promoting treatments are ineffective. We hypothesized that cognitive training during the adolescent period of neuroplastic development can tune compromised neural circuits to develop in the service of adult cognition and attenuate schizophrenia-related cognitive impairments that manifest in adulthood. We report, using neonatal ventral hippocampus lesion rats (NVHL), an established neurodevelopmental model of schizophrenia, that adolescent cognitive training prevented the adult cognitive control impairment in NVHL rats. The early intervention also normalized brain function, enhancing cognition-associated synchrony of neural oscillations between the hippocampi, a measure of brain function that indexed cognitive ability. Adolescence appears to be a critical window during which prophylactic cognitive therapy may benefit people at risk of schizophrenia.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Avoidance Learning
  • Brain Waves / drug effects
  • Cell Count
  • Cognition Disorders / etiology*
  • Cognition Disorders / prevention & control*
  • Cognitive Behavioral Therapy / methods*
  • Conditioning, Operant / drug effects
  • Developmental Disabilities / chemically induced
  • Developmental Disabilities / complications*
  • Developmental Disabilities / pathology
  • Disease Models, Animal
  • Electroencephalography
  • Excitatory Amino Acid Agonists
  • Female
  • Functional Laterality / drug effects
  • Gene Expression Regulation / physiology
  • Hippocampus / drug effects
  • Hippocampus / injuries
  • Hippocampus / metabolism
  • Ibotenic Acid / toxicity
  • Male
  • Maze Learning
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Parvalbumins / metabolism
  • Pregnancy
  • Rats
  • Rats, Long-Evans
  • Schizophrenia / chemically induced
  • Schizophrenia / complications*
  • Schizophrenia / pathology

Substances

  • Excitatory Amino Acid Agonists
  • Parvalbumins
  • Ibotenic Acid