Optogenetic stimulation of medial prefrontal cortex excites GABAergic cells in the nucleus accumbens and hippocampus of Wistar-Kyoto rats exposed to chronic mild stress.

Abstract

High frequency optogenetic stimulation (OGS) of prelimbic cortex (PLC) has been reported to exertantidepressant-like effects in the chronic mild stress model of depression in Wistar Kyoto (WKY) rats, which arenon-responsive to antidepressant drugs. Here we have examined the effect of OGS on activity in the PLC and intwo other regions implicated in depression, the nucleus accumbens (NAc) and hippocampus (HPC). OGSwas applied to the PLC of WKY rats using the same stress schedule, and the identical placement, virus infectionand stimulation parameters, used in the earlier behavioural experiments. Confocal microscopy was used to identifycells co-expressing the immediate early gene c-Fos and markers of GABAergic (GAD) and glutamatergic (CaMKII)neurons. Stress decreased sucrose intake, which was restored by OGS. Stress also caused an overalldecrease in Fos expression in the structures examined. In stressed animals, but not in non-stressed controls, OGSin mPFC increased the number of Fos+ cells in both the core and shell of the NAc (where the vast majority of cellsare GABAergic), and increased the number and proportion of active GABAergic, but not glutamatergic, cells indorsal and ventral HPC and dentate gyrus. We conclude that OGS of PLC has a net excitatory effecton outputs from the PLC, leading to an overall inhibitory effect in structures innervated (NAc and HPC).