Abstract
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.
Highlights
The striatum is the primary input nuclei of the basal ganglia
PV::Cre mice injected with AAV9-EF1α-DIOmCherry or AAV9-EF1α-DIO-ChR2-mCherry in the NAc core (NAcc) were placed in one compartment of conditioned place preference (CPP) apparatus, and received optical stimulation through optical fibers placed over the NAcc to activate ChR2 in PV+ interneurons during place conditioning (Figures 1A–C)
During subsequent CPP test, NAccPV:ChR2 mice showed significant place preference as they spent more time in the stimulation-paired compartment than NAccPV: mCherry mice did (Figure 1D, Ftreatment × session(1,28) = 10.244, p = 0.003, two-way RM Analysis of Variance (ANOVA)). These data showed that optogenetic activation of ChR2 in accumbal PV+ interneurons induced CPP, suggesting activation of these GABAergic interneurons in the NAcc supports rewarding and approaching behavior
Summary
The ventral striatum, known as the nucleus accumbens (NAc), plays a critical role in processing motivated behavior and reward-related learning (Floresco, 2015). SPNs are classically divided into two approximately sized populations based on their projection targets and expression of dopamine receptors. SPNs in direct pathway (dSPNs) mainly express Gs/olf-coupled dopamine D1 receptors and send dense projections to the VTA. SPNs in indirect pathway (iSPNs) mainly express Gi/o-coupled dopamine D2 receptors and send axons to the ventral pallidum (VP; Soares-Cunha et al, 2016). Local GABAergic signaling strongly regulates the activity of both dSPNs and iSPNs in striatum (Nisenbaum and Berger, 1992; Wilson, 2007), the roles of GABAergic interneurons in regulating the NAc output pathways and the behavioral responses to psychostimulants remain poorly understood
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