PBN-PVT projections modulate negative affective states in mice.

Xiao-Xiao Hua,Yan Wang,Ya-Bing Zhu,Ling Zhang,Ming-Zhe Liu,Peng-Fei Liu,Ling Xu,Rui Zhang,Jin-Bao Li,Di Mu

doi:10.7554/elife.68372

Abstract

Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus (PBN) and thalamic paraventricular nucleus (PVT) are critical for modulating affective states in mice. However, the functional roles of PBN-PVT projections in modulating affective states remain elusive. Here, we show that PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with PVT neurons. Activation of the PBN-PVT pathway induces robust behaviors associated with negative affective states without affecting nociceptive behaviors. Inhibition of the PBN-PVT pathway reduces aversion-like and fear-like behaviors. Furthermore, the PVT neurons innervated by the PBN are activated by aversive stimulation, and activation of PBN-PVT projections enhances the neuronal activity of PVT neurons in response to the aversive stimulus. Consistently, activation of PVT neurons that received PBN-PVT projections induces anxiety-like behaviors. Thus, our study indicates that PBN-PVT projections modulate negative affective states in mice.

Highlights

Threat and injury often induce defensive behaviors, such as flight, freezing, hiding (Öhman and Mineka, 2001), and negative affective states, such as fear and anxiety (Jimenez et al, 2018)
It has been shown that the paraventricular nucleus (PVT) receives input from the parabrachial nucleus (PBN) (Chiang et al, 2020; Li and Kirouac, 2012), the detailed morphology of PBN-PVT
We found that optogenetic activation of PBN projection fibers evoked excitatory postsynaptic currents (EPSCs) in 34 of 52 PVT neurons

Summary

Introduction

Threat and injury often induce defensive behaviors, such as flight, freezing, hiding (Öhman and Mineka, 2001), and negative affective states, such as fear and anxiety (Jimenez et al, 2018). Such behavioral adaptations and psychological responses are essential for animal survival, and understanding their mechanisms is of great interest. Neurons in the dorsal division of the PBN projecting to the ventromedial hypothalamus (VMH) and PAG mediate escape behaviors. Neurons in the external lateral division of the PBN projecting to the bed nucleus of the stria terminalis (BNST) and the CeA mediate aversion and avoidance memory (Chiang et al, 2020).

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