Neuropeptide S Attenuates the Alarm Pheromone-Evoked Defensive and Risk Assessment Behaviors Through Activation of Cognate Receptor-Expressing Neurons in the Posterior Medial Amygdala.

Yu-Feng Shao,Yi-Ping Hou,Xing-Wen Yang,Jing Li,Chao-Yu Dong,Can Wang,Fu-Qiang Xu,Xiao-Ping Rao,Jun-Fan Xie,Hua-Dong Wang,Yan-Li Ren

doi:10.3389/fnmol.2021.752516

Abstract

Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1–1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val5]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val5]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.

Highlights

In their continuous struggle for survival, predator and prey species interact to maximize the likelihood of finding food or avoiding being eaten
The present study demonstrated that central action of Neuropeptide S (NPS) reversed the increased defensive and risk assessment behaviors, and the reduced exploratory behaviors evoked by Alarm pheromone (AP) (Figures 2, 3, and Supplementary Figure 1)
0.1 nmol of NPS significantly attenuated the increased head-out (Figures 2C, 3C) and decreased outside durations (Figures 2A, 3A) of the mice exposed to AP, but it did not significantly affect the other behaviors it tended to reduce concealment (Figure 3B), suggesting that the minute amount of NPS enables the stressed animals to alleviate the risk assessment behavior and partially improve defensive and exploratory behaviors, but it is not yet enough to enable them to move freely in open arena like control animals (Figures 2D, 3D, and Supplementary Figure 1)

Summary

Introduction

In their continuous struggle for survival, predator and prey species interact to maximize the likelihood of finding food or avoiding being eaten. Alarm pheromone (AP), released from conspecific animal who is under the threatening situation (Ono et al, 2003; Brechbühl et al, 2008, 2013), relays the presence of danger and possibly plays an important role in increasing overall species fitness (Kiyokawa et al, 2006; Brechbühl et al, 2008). The GG is a part of main olfactory system (MOS), and is an arrow-shaped neuronal structure and situates underneath the dorsal cartilage of the anterior tip of the nasal cavity. Their axons’ targets locate outside but around the rostral part of the AOB (Fuss et al, 2005; Koos and Fraser, 2005; Roppolo et al, 2006). That the olfactory signals from the MOS and AOS converge on the MePD and MePV of medial amygdaloid nucleus (MeA) should be involved in regulation of social behaviors induced by social pheromones (Keshavarzi et al, 2015; Matsuo et al, 2015)

Methods

Results

Conclusion