224. Putative thalamic terminals are decreased in the prefrontal cortex in schizophrenia

Abstract

Recent studies have reported decreased neuron number in the mediodorsal thalamic nucleus (MDTN), the principal source of thalamic projections to the prefrontal cortex (PFC), in subjects with schizophrenia. In thalamic relay nuclei, the calcium binding protein parvalbumin (PV) is present in the neurons that provide the major thalamic projection to the cortical layers deep 3-4. In ultrastructural studies of area 9 in monkey PFC, we found PV immunoreactivity in axon terminals forming Gray’s Type I (excitatory) synapses exclusively in layers deep 3 and 4 (Melchitzky, et al., J Comp Neurol, 1998). In order to test the hypothesis that schizophrenia is associated with altered thalamic inputs to PFC, we examined PV-immunoreactive varicosities in PFC area 9 of 20 pairs of schizophrenic and control subjects matched for age, sex, and postmortem interval. Systematic random sampling techniques were used to quantify the density of PV-immunoreactive varicosities in 1 μm thick sections. The density of PV-positive varicosities did not differ between schizophrenic and control subjects in layers 2-superficial 3, whereas a significant (p = .006) decrease (24%) was found in layers deep 3-4 of the schizophrenic subjects. PV-positive axon terminals from cortical local circuit neurons are present in both superficial and middle cortical layers. Since the reduction in PV-labeled varicosities was present only in the middle zone, these findings suggest that the PV-positive terminals from thalamic relay nuclei are decreased in schizophrenia. These data are convergent with the results of other postmortem studies demonstrating altered thalamic-prefrontal cortical connectivity in schizophrenia.