Glutamate is packaged and released into the synaptic cleft, activating ionotropic and metabotropic glutamate receptors that mediate numerous physiological activities. Glutamate is packaged into vesicles by a family of vGLUTs expressed in glutamatergic (vGLUT1-2) and cholinergic (vGLUT3) neurons. While the function of vGLUT3 in cholinergic neurons is not known, the vGLUTs are a good marker for identification and evaluation of presynaptic glutamatergic function in the brain. Using in situ hybridization, I am examining expression of the vGLUTs in the hippocampus (HPC), entorhinal cortex (ERC), intermediate temporal gyrus (ITG) and medial temporal gyrus (MTG) in schizophrenia, bipolar disorder, and major depressive disorder. Changes in expression of vGLUT1 and vGLUT2 transcripts were limited to cortical regions in bipolar disorder and major depressive disorder. We did not find changes in vGLUT1 or 2 in the HPC, ERC, MTG or ITG in schizophrenia. These data support our hypothesis that alterations of glutamatergic function are present in mood disorders. Ongoing studies include evaluation of vGLUT3 transcript expression in the medial temporal lobe structures in these illnesses.

Rob McCullumsmith