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

Abstract

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-like avoidance when mice are under anxiogenic situations. Firing rates of sNAc PV neurons were negatively correlated to exploration time in open arms (threatening environment). In addition, sNAc PV neurons exhibited high excitability in a chronic stress mouse model, which generated excessive maladaptive avoidance behavior in an anxiogenic context. We also discovered a novel GABAergic pathway from the anterior dorsal bed nuclei of stria terminalis (adBNST) to sNAc PV 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 adBNST GABA → sNAc PV synapses, which in turn explains the hyperexcitability of sNAc PV neurons on stressed models. Therefore, activation of these GABAergic afferents in sNAc rescued the excessive avoidance behavior related to an anxious state. Finally, we identified that the majority GABAergic input neurons, which innervate sNAc PV cells, were expressing somatostatin (SOM), and also revealed that coordination between SOM-and PV-cells functioning in the BNST → NAc circuit has an inhibitory influence on anxiety-like responses. Our findings provide a potentially neurobiological basis for therapeutic interventions in pathological anxiety.

Parvalbumin interneurons in the nucleus accumbens regulate impairment of risk avoidance in DISC1 transgenic mice

“…Before tamoxifen injection, theta (4-8 Hz) power was significantly lower on the open arms than that on the closed arms (Fig. 3A), which is consistent with our previously reported findings in wild-type mice [17]. However, after tamoxifen injection, LFP power in the theta band was not predictive of whether the DISC1-N TM mice were on the open arms or closed arms (Fig.…”

“…What's more, our previous work has shown that PV interneurons in the NAc regulate the performance of chronically stressed mice in the EPM [17]. Thus, we propose that PV interneurons in the NAc are response for the abnormal risk avoidance behavior of DISC1-N TM mice.…”

“…Our previous work showed that neurons in the NAc can control behavioral states and regulate mouse performance on the EPM [17]. Moreover, the NAc is considered to be an interface between cognition and emotion [26].…”

“…We do know that abnormal development and impaired PV interneuron function have been found in mice with DISC1 truncation [15,16]. Previous work from our group has suggested that activity of NAc PV neurons are required for anxiety-like behavior [17].…”

An Infrared Touch System for Automatic Behavior Monitoring

“…Typically, whole trials are recorded in which the position of the animal is tracked, and much analysis is done post hoc [1][2][3]. In many behavioral paradigms, such as the elevated plus maze (EPM) [4][5][6][7] and the two-chamber tests [8][9][10], the only information extracted from the video to describe animal behavior is its trajectory, or the position of the animal in each frame. However, analysis of video data requires a large amount of computational power, which puts demands on both hardware and the algorithms required to analyze animal behavior in real time.…”