Role Of Neuropeptide S In Olfactory Regulation Of Mice

Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the GPR154which now referred to as NPS receptors (NPSR). High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. So far, the effects of NPS on olfactory regulation and the mechanism involved remain unknown. The aim of present study was undertaken to reveal the effect of NPS-NPSR system on olfactory function and the potential mechanism involved in olfactory regulation.Firstly, olfactory behaviors detected with buried food test and olfactory habituation/dishabituation test were employed to investigate the effects of intracerebroventricular (i.c.v.) injection of NPS or co-injection of NPSR antagonist on olfactory function in mice. NPS-induced active neurons in olfactory cortex were labeled with c-Fos immunohistochemistry. In addition, dual-immunofluorescence was used to identify NPS induced c-Fos immuneractive (ir) neurons that also bear NPSR. Whole cell patch clamp was used to survey the effects of NPS on potential of neuronal membrane in the olfactory cortex. Secondly, a model of olfactory impaired by allergic rhinitis (AR) was employed to evaluate the ameliorative effect of NPS on olfaction in mice. Olfactory bulb local field potential (LFP), power spectral analysis of LFP. and olfactory mucosa pathology were used to reveal the modulated effect and pathway of NPS on olfactory abilities under the AR pathological condition.Results:NPS (0.1-1nmol) i.c.v injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks, as compared with vehicle-treated mice. NPS facilitated olfactory ability most at the dose of0.5nmol, Which could be blocked by co-injection of NPSR antagonist [D-Val5]NPS (40nmol). NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as (?)mpared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON), piriform cortex (Pir), ventral tenia tecta (VTT), the anterior cortical amygdaloid nucleus (ACo) and lateral entorhinal cortex (LEnt). The percentage of Fos-ir neurons that also express NPSR were88.5%and98.1%in the AON and Pir, respectively. NPS predominantly depolarized the AON and Pir neurons in whole cell patch clamp recording.AR mice showed that olfactory abilities declined, infiltrated eosinophils within olfactory submucosa increased, and the power of delta band (0-3.9Hz) of olfactory bulb LFP decreased. NPS (0.1-1nmol) i.c.v. administration significantly enhanced olfactory abilities, and the power of delta band of olfactory bulb LFP at the dose of1nmol in AR mice. However, the pathological variation within olfactory mucosa and allergic symptoms in the AR mice were unimproved after NPS (1nmol) i.c.v. injection.Conclusion:NPS facilities mice olfactory function through activation of the neurons bearing NPSR in the olfactory cortex. NPS promotes olfactory abilities in AR mice via central pathway of olfactory regulation.