Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability.

Laifu Li,Li-Zi Zhang,Yi-Tong Li,Rui Jia,Zi-Jian Lv,Yu-Feng Xun,Yu-Ting Zhang,Huan Ma,Fa-Dao Tai,Wen-Juan Hou,Wei Yuan,Zhi-Xiong He

doi:10.7554/elife.67638

Abstract

Consolation is a common response to the distress of others in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. By using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nucleus (DR) or optogenetic inhibition of serotonin (5-HT) terminals in the anterior cingulate cortex (ACC) significantly decreased allogrooming time in the consolation test and reduced sociability in the three-chamber test. The release of 5-HT within the ACC and the activity of DR neurons were significantly increased during allogrooming, sniffing, and social approaching. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided the first direct evidence that DR-ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability.

Highlights

Consolation behavior, which is referred to as an increase in affiliative contact toward a distressed individual by an uninvolved bystander, is an important component of the social capabilities of humans (de Waal and Preston, 2017; Field et al, 2009)
The retrograde tracer cholera toxin subunit B (CTB) was injected into the anterior cingulate cortex (ACC), followed by immunofluorescence staining of the dorsal raphe nucleus (DR) sections with tryptophan hydroxylase 2 (TPH2), a marker of 5-HTergic neurons
We have demonstrated a crucial role for the DR!ACC 5-HTergic neural circuit in the regulation of consolation-like behaviors and sociability in mandarin voles for the first time

Summary

Introduction

Consolation behavior, which is referred to as an increase in affiliative contact toward a distressed individual by an uninvolved bystander, is an important component of the social capabilities of humans (de Waal and Preston, 2017; Field et al, 2009). Our recent study has indicated that 5HT1A receptors within the ACC are involved in consolation deficits induced by chronic social defeat stress in mandarin voles (Li et al, 2020). Direct modulation of the DR!ACC 5-HTergic circuit to investigate its functional role in consolation-like behaviors is interesting and meaningful. We first investigated the function of DR!ACC 5-HTergic circuits in consolation-like behaviors using optogenetic and chemogenetic approaches. To provide more direct evidence, we monitored ACC 5-HT release and DR neuron activities during this behavior by using in vivo fiber photometry. We used chemogenetics plus pharmacological approaches to investigate which types of 5-HT receptors in the ACC are involved in consolation-like behaviors in mandarin voles. In general, a pro-social behavior, some social behaviors were investigated during the tests

Results

Discussion

Materials and methods

Funding Funder