Background
Cerebral cortical GABAergic interneuron dysfunction is hypothesized to lead to cognitive deficits co-morbid with human neuropsychiatric disorders, including schizophrenia, autism and epilepsy. We have previously shown that mice that harbor mutations in the Plaur gene, which is associated with schizophrenia, have deficits in frontal cortical parvalbumin expressing interneurons. Plaur mice have impaired reversal learning, similar to deficits observed in patients with schizophrenia.
Methods
We examined the role of parvalbumin interneurons in orbitofrontal cortex (OFC) during reversal learning by recording single unit activity from 180 control and 224 Plaur mouse neurons during a serial reversal task. Neural activity was analysed during correct and incorrect decision choices and reward receipt.
Results
Neurons in control mice exhibited strong phasic responses both during discrimination and reversal learning to decisions and rewards, and the strength of the response was correlated with behavioral performance. Although baseline firing was significantly enhanced in Plaur mice, neural selectivity for correct or erroneous decisions was diminished and not correlated with behaviour, and reward encoding was downscaled. In addition, Plaur mice showed a significant reduction in the number of neurons that encoded expected outcomes across tasks phases during the decision period.
Conclusions
These data indicate that parvalbumin interneurons are necessary for the representation of outcomes in OFC. Deficits in inhibition blunt selective neural firing during key decisions, contributing to behavioral inflexibility. These data provide a potential explanation for disorders of cognitive control that accompanies the loss of these GABAergic interneurons in human neuropsychiatric disorders, such as autism, epilepsy, and schizophrenia.