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Parvalbumin (PV) expressing GABAergic interneurons provide large source of GABA to spiny projection neurons (SPNs) in the striatum. However, the roles of PV +  interneurons in the regulation of SPNs in the ventral striatum and emotional states are largely unknown. Here, we investigated whether stimulation of ventral striatal (accumbal) PV +  interneurons would drive emotional valence in mice. We found that during conditioned place preference (CPP) training, activation of accumbal PV +  interneurons evoked place preference while suppressing them resulted in conditioned place aversion (CPA). Activation of PV +  interneurons during place conditioning increased  Fos  expression in SPNs in the direct pathway (dSPNs) and impaired lithium chloride-induced CPA. Activation of dSPNs and SPNs in the indirect pathway (iSPNs) induced CPP and CPA, respectively; conversely, suppression of dSPNs or iSPNs induced CPA or CPP. In addition, activation or suppression of calretinin-expressing (CR) GABAergic interneurons did not induce place preference or aversion. These data suggest that PV +  interneurons can bidirectionally determine the emotional valence through their regulation of accumbal SPN activities and raise the possibility that manipulation of PV +  interneuron activity may have the potential to alter emotional valence and treat related mental disorders.

Parvalbumin Interneurons Determine Emotional Valence Through Modulating Accumbal Output Pathways