Inhibitory DREADD manipulation induces convulsions in the secondary but not the primary somatosensory cortex,...

Among the cortical circuits thought to be essential for sensorimotor processing, the secondary somatosensory cortex (S2) is particularly poorly understood. The S2 is attracting increasing attention and is expected to be studied from various perspectives. Chemogenetics is one of the cooperative tools for elucidating its function. We observed unexpected convulsions in rats when their S2 was manipulated using an inhibitory Designer Receptors Exclusively Activated by Designer Drug (DREADD) (hM4D(Gi)), which was expressed under the synapsin promoter and activated by deschloroclozapine (DCZ). No convulsions were observed when administering saline to these rats or when administering DCZ to rats expressing the DREADD under the CaMKIIα promoter. No convulsions were observed when the primary somatosensory cortex (S1) was manipulated using the same Syn promoter-driven system. Using the hDlx enhancer, manipulation of both the S1 and the S2 induced convulsions. These findings suggest that the convulsion induction was not due to simple suppression of cortical output, but rather, it likely resulted from a disruption of the excitation-inhibition balance in the S2. The difference in susceptibility between the S1 and the S2 may reflect differences in circuit complexity and/or cellular type composition. The results emphasize the importance of promoter selection in chemogenetic studies and suggest that the S2 may play a critical role in maintaining sensorimotor stability.NEW & NOTEWORTHY Unexpected convulsions were induced by inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the secondary but not the primary somatosensory cortex when they were expressed under the synapsin promoter. Although the underlying detailed mechanism remains unclear, the finding underscores the importance of promoter selection in chemogenetic studies and offers novel insights into the functional role of the secondary somatosensory cortex (S2) in sensorimotor integration.