Effects of a mediodorsal thalamus lesion on prefrontal inhibitory circuitry: implications for schizophrenia

Background Schizophrenia is associated with both reductions in prefrontal cortical (PFC) inhibitory markers and in neuron number in the mediodorsal thalamus (MDTN), which provides excitatory input to the PFC. To investigate the potential pathophysiologic relationship between these observations, we sought to provide experimental evidence that a reduction in MDTN neurons can produce decreased PFC glutamate decarboxylase (GAD67) mRNA expression. Methods Ibotenic acid was injected bilaterally into MDTN in rats. Four weeks later, thalamic lesion volumes were assessed stereologically, and PFC GAD67 mRNA expression was measured using in situ hybridization. Results Selective MDTN lesions produced no changes in PFC GAD67 mRNA expression, either overall or by cortical layer, and lesion volumes and GAD67 mRNA expression were not correlated. Conclusions In rats, a substantial lesion of MDTN neurons does not decrease PFC GAD67 mRNA expression. These results do not support the hypothesis that decreased PFC GAD67 mRNA expression in schizophrenia is attributable to a reduction in MDTN neuron number.