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A new GABAergic projection from the BNST onto accumbal parvalbumin neurons controls anxiety

By Qian Xiao, Xinyi Zhou, Pengfei Wei, Li Xie, Yaning Han, Bifeng Wu, Jie Wang, Aoling Cai, Fuqiang Xu, Yi Lu, Jie Tu, Liping Wang

Posted 14 Sep 2019
bioRxiv DOI: 10.1101/767228

The prevailing view is that parvalbumin (PV) interneurons play modulatory roles in emotional response through local medium spiny projection neurons (MSNs). Here, we show that PV activity within the nucleus accumbens shell (sNAc) is required for producing anxiety-related avoidance when mice are under anxiogenic situations; sNAcPV neurons exhibited high excitability in chronically stressed mice model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic projections from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAcPV neurons; optogenetic activation of these afferent terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, we further demonstrated that chronic stressors attenuated the inhibitory synaptic transmission at adBNSTGABA-sNAcPV synapses, which in turn explains the hyperexcitability of sNAcPV neurons on stressed models; therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to anxious state. Our findings reveal the coordination between BNST and NAc through an inhibitory architecture in controlling of anxiety-related response and provide a neurobiological basis for therapeutic interventions in pathological anxiety.

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