Developmental emergence of reelin deficits in the prefrontal cortex of Wistar rats reared in social isolation

As the pathophysiological mechanism(s) of many neuropsychiatric disorders relate to GABAergic interneuron structure and function, we employed isolation rearing of Wistar rats as a model to correlate developmental emergence of cognitive deficits with the expression of reelin-producing interneurons in the medial prefrontal cortex (PFC). Prepulse inhibition deficits emerged at postnatal day 60 and persisted into adulthood. Paralleling the emergence of these neurobehavioural deficits was an increase in reelin production and reelin-immunopositive cells in layer I of the PFC and this later became significantly reduced at postnatal day 80. Cells expressing reelin immunoreactivity in a horizontal orientation were mainly located to the upper regions of layer I whereas those with a vertical orientation, whose arbors extend into cortical layers II and III, were more numerous in the lower regions of layer I and became significantly dysregulated during postnatal development. No behavioural deficits or altered reelin expression was observed at postnatal days 30 or 40. Developmental emergence of neurobehavioural and reelin deficits in isolation reared animals is proposed to reflect maladaptive wiring within the medial prefrontal cortex during a critical maturation period of this circuitry.