Hypocretin/orexin peptides alter spike encoding by serotonergic dorsal raphe neurons through two distinct mechanisms that increase the late afterhyperpolarization

Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N. Ross, Christopher S. Leonard

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca2+ influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons. Intracellular phospholipase C inhibition (U73122) blocked the entire oeAHP, but neither component was sensitive to PKC inhibition or altered PKA signaling, unlike classical sAHPs. The enhanced SK current did not depend on IP3-mediated Ca2+ release but resulted from A-current inhibition and the resultant spike broadening, which increased Ca2+ influx and Ca2+-induced-Ca2+ release, whereas the slower component was insensitive to these factors. Functionally, the oeAHP slowed and stabilized orexin-induced firing compared with firing produced by a virtual orexin conductance lacking the oeAHP. The oeAHP also reduced steady-state firing rate and firing fidelity in response to stimulation, without affecting the initial rate or fidelity. Collectively, these findings reveal a new orexin action in serotonergic raphe neurons and suggest that, when orexin is released during arousal and reward, it enhances the spike encoding of phasic over tonic inputs, such as those related to sensory, motor, and reward events.

本文言語English
ページ(範囲)10097-10115
ページ数19
ジャーナルJournal of Neuroscience
36
39
DOI
出版ステータスPublished - 2016 9 28

ASJC Scopus subject areas

  • Neuroscience(all)

フィンガープリント 「Hypocretin/orexin peptides alter spike encoding by serotonergic dorsal raphe neurons through two distinct mechanisms that increase the late afterhyperpolarization」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル