Investigation of gaba-ergic interneuron-localized gene expression in the subgenual cingulate cortex of postmortem subjects diagnosed with bipolar disorder and schizophrenia

Krolewski DM, Waselus M, Kumar V, Myers RM, Lee FS, Barchas JD, Schatzberg A, Bunney WE, Akil H, Watson SJ
50th Annual Meeting of the Society for Neuroscience, Virtual. 2021.

Abstract

The human anterior cingulate cortex can be neuroanatomically subdivided, in relation to the corpus callosum, into dorsal (ACg) and ventral subgenual (SCg) components and is collectively well known to be involved in the regulation of emotional behaviors pertinent to mental illness. In a recently completed internal study, our laboratory has observed significant distributional mRNA differences related to GABA-ergic interneuron-localized transcripts, diagnosis, and anatomically distinct subregions within the ACg involving Brodmann’s areas (BA) 24 and 32. To further characterize the cingulate cortex, the goal of the current study is to measure mRNA transcripts reflecting the same interneuron subpopulations within the SCg which also employ contrasting synaptic pyramidal cell connectivity. The latter include non-overlapping subpopulations identified by differential expression of parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP). Our experimental methods combined the in-situ hybridization (ISH) technique using radiolabeled cRNA probes with 10 ɥm fresh-frozen SCg sections from control (n=20), schizophrenia (n=16), and bipolar disorder (n=22) subjects. Gray-scale optical density values are being used to determine potential diagnosis-related gene expression differences in PV, SST, and VIP mRNA spanning SCg subdivisions that include BA 33, 25, and ventral area 24. The results of this study will further our understanding how information processing may be dysregulated by way of GABA-ergic interneuron function in the SCg of bipolar and schizophrenic patients.