Neuropeptide S Ameliorates The Dysfunction Of Olfactory Spatial Memory In Mice

Olfaction and olfactory memory for rodents are the most vital perception, and play a crucial role in social behaviors including foraging, avoiding predators and mating. Neuropeptide S (NPS) has been identified to improve visual spatial memory in mice. Our previous studies have demonstrated that NPS promotes olfactory function, and ameliorates allergic rhinitis-induced olfactory dysfunction in mice. We suppose that NPS and its receptor (NPS-NPSR) system is involved in the amelioration of the dysfunction of olfactory spatial memory. The present study is designed to detect the effect of NPS-NPSR system on the dysfunction of olfactory spatial memory and the potential mechanism involved in.Methods:Scopolamine (2 mg/Kg), an antagonist of cholinergic M receptor, or MK-801 (0.1 mg/Kg), an antagonist of NMD A receptor was injected intraperitoneally (i.p.) to induce a model of spatial memory impairment in mice. A computer-assisted 4-hole-board spatial memory test was used to detect the ameliorative effect of NPS on the dysfunction of olfactory spatial memory. The neural activity induced by NPS was defined with c-Fos immunohistochemistry. In addition, dual-immunofluorescence was employed to delineate NPS-induced Fos immunoreactive (-ir) neurons that also bear NPSR.Results:Intracerebroventricular (i.cv.) injection of NPS (0.5 nmol) significantly ameliorates the undiscriminating abilities on switched odors in mice-treated with scopolamine or MK-801, respectively. The ameliorative effect of NPS (0.5 nmol) on olfactory spatial memory impairment was blocked by 40 nmol of NPSR antagonist [D-Val5]NPS.Ex-vivo Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex including the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentage of Fos-ir neurons that also bear NPSR were 91.3%,86.5% and 90.0% in the S, PrS and PaS respectively.Conclusions:NPS ameliorates the dysfunction of olfactory spatial memory in mice via selective activation of the neurons bearing NPSR in the subiculum complex.