Glutamatergic gene expression is specifically reduced in thalamocortical projecting relay neurons in schizophrenia

Background—Impairment of glutamate neurons which relay sensory and cognitive information from the medial dorsal thalamus to the dorsolateral prefrontal cortex and other cortical regions may contribute to the pathophysiology of schizophrenia. In this study we have assessed the cellspecific expression of glutamatergic transcripts in the medial dorsal thalamus. Methods and Materials—We used laser-capture microdissection to harvest two populations of medial dorsal thalamic cells, one enriched with glutamatergic relay neurons, and the other with GABAergic neurons and astroglia, from postmortem brains of subjects with schizophrenia (n=14) and a comparison group (n=20). Quantitative polymerase chain reaction (QPCR) of extracted RNA was used to assay gene expression in different cell populations. Results—The transcripts encoding the ionotropic glutamate receptor subunits NR2D, GluR3, GluR6, GluR7, and the intracellular proteins GRIP1 and SynGAP1 were significantly decreased in relay neurons but not in the mixed glial and interneuron population in schizophrenia. Discussion—Our data suggest that reduced ionotropic glutamatergic expression occurs selectively in neurons giving rise to the cortical projections of the medial dorsal thalamus in schizophrenia, rather than in thalamic cells which function locally. Our findings indicate that glutamatergic innervation is dysfunctional in the circuitry between the medial dorsal thalamus and cortex.