title: Activation of neuropeptide S-expressing neurons in the locus coeruleus by corticotropin-releasing factor.
abstract: A recently discovered neurotransmitter system, consisting of neuropeptide S (NPS), NPS receptor, and NPS-expressing neurons in the brain stem, has received considerable interest due to its modulating influence on arousal, anxiety and stress responsiveness. Comparatively little is known about the properties of NPS-expressing neurons. Therefore in the present study, a transgenic mouse line expressing enhanced green fluorescent protein (EGFP) in NPS neurons was used to characterize the cellular and functional properties of NPS-expressing neurons located close to the locus coeruleus. Particular emphasis was on the influence of corticotropin-releasing factor (CRF), given previous evidence of stress-related activation of the NPS system. Upon acute immobilization stress, an increase in c-fos expression was detected immunocytochemically in brain stem NPS-EGFP neurons that also expressed the CRF receptor 1 (CRF1). NPS-EGFP neurons were readily identified in acute slice preparations and responded to CRF application with a membrane depolarization capable of triggering action potentials. CRF-induced responses displayed pharmacological properties indicative of CRF1 that were mediated by both a reduction in membrane potassium conductance and an increase in a non-specific cation conductance different from the hyperpolarization-activated cation conductance Ih, and involved protein kinase A signalling. In conclusion, stress exposure results in activation of brain stem NPS-expressing neurons, involving a CRF1-mediated membrane depolarization via at least two ionic mechanisms. These data provide evidence for a direct interaction between the CRF and the NPS system and thereby extend previous observations of NPS-modulated stress responsiveness towards a mechanistic level.
authors.affiliation: H.-C. Pape: Institute of Physiology I; Robert-Koch-Str. 27a, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Jüngling
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Liu
authors.forename: Jörg
authors.initials: J
authors.lastname: Lesting
authors.forename: Philippe
authors.initials: P
authors.lastname: Coulon
authors.forename: L
authors.initials: L
authors.lastname: Sosulina
authors.forename: Rainer K
authors.initials: RK
authors.lastname: Reinscheid
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000200:Action Potentials; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D055724:Electrophysiological Phenomena; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D007103:Immobilization; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological
chemical_list: D009479:Neuropeptides; C485184:enhanced green fluorescent protein; C539972:neuropeptide S, mouse; D049452:Green Fluorescent Proteins; D003346:Corticotropin-Releasing Hormone