Distinct Hypothalamic Paraventricular Nucleus Inputs to the Cingulate Cortex and Paraventricular Thalamic Nucleus Modulate Anxiety and Arousal.

Ying Liu,Shuang Li,Bo Rao,Haibo Xu,Linlin Bi,Jie Wang,Ning Zheng

doi:10.3389/fphar.2022.814623

Abstract

Insomnia and anxiety are two common clinical diseases that threaten people’s physical and mental health. Insomnia and anxiety may share some similar underlying neural circuit mechanisms in the brain. In this study, we combine techniques including chemo-fMRI, optogenetics, and chemogenetics to reveal that the glutamatergic neurons of the paraventricular hypothalamic nucleus (PVN) regulate both anxiety and arousal through two different downstream neural circuits. Optogenetic activation of the PVN-cingulate cortex (Cg) neural circuit triggers anxiety-like behaviors in mice without affecting the wakefulness, while optogenetic activation of the PVN-paraventricular thalamic nucleus (PVT) neural circuit promotes wakefulness in mice without affecting anxiety-like behaviors. Our research reveals that PVN is a key brain area for controlling anxiety and arousal behaviors. We also provide a neurological explanation for anxiety disorder and insomnia which may offer guidance for treatments including drugs or transcranial magnetic stimulation for the patients.

Highlights

Insomnia and anxiety are both clinically common diseases that endanger human health
Research has shown that the paraventricular hypothalamic nucleus (PVN) neurons have reciprocal axonal projections with dozens of brain areas, including the ventromedial hypothalamus (VMH), the dorsomedial hypothalamus (DMH), the preoptic area (POA), the lateral septum (LS), the paraventricular thalamic nucleus (PVA), the lateral parabrachial nucleus (LPB), the pyramidal cell layer of the hippocampus, and the periaqueductal gray (PAG) (Luo et al, 2019)
Taking the PVN as the seed, it was found that the functional connectivity (FC) between the PVN and the olfactory nucleus, the Cg, the paraventricular thalamic nucleus (PVT), the periaqueductal gray nucleus (PAG), the motor cortex, the caudateputamen, and hippocampus increased after CNO injection (Figure 1D; Table 1)

Summary

Introduction

Insomnia and anxiety are both clinically common diseases that endanger human health. Healthy sleep is very important for people’s physical and mental health. There is an inseparable relationship between sleep disorders and anxiety disorders. Sleep problems may lead to anxiety and depression, and anxiety is often experienced along with insomnia (Fuller et al, 1997; Staner, 2003). Sleep disorder is one of the core symptoms of mental illness such as anxiety and depression. Sleep quality can be used to predict anxiety in veterans with posttraumatic stress disorder (PTSD) (Mantua et al, 2018), suggesting that insomnia and anxiety disorders may share similar underlying neural circuit mechanisms. It is of great significance to explore the similarities and differences between the neural circuits that regulate these two behaviors

Methods

Results

Conclusion