Penzo, M. a., Robert, V., & Li, B.


Mario A. Penzo, Vincent Robert, Jason Tucciarone, Dimitri De Bundel {, MinghuiWang1, Linda Van Aelst, Martin Darvas, Luis F. Parada, Richard D. Palmiter,MiaoHe, Z. Josh Huang &Bo Li.




Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psycho- logical stressors1–3 . However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression4,5 . Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM1) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervateSOM1neurons in the CeL, and stimulation of PVT afferents facilitatedSOM1neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression5,6 . Notably, PVT modulation ofSOM1CeLneuronswas mediated by activation of the brain- derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either PVTor infusion of BDNF into the CeL enhanced fear learning and elicited Trkb Bdnf in the inSOM1CeLneuronsimpairedfear conditioning, while unconditioned fear responses. Our results demonstrate that the PVT– CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.


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