Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. - Archive ouverte HAL Access content directly
Journal Articles Journal of Neuroscience Year : 2009

Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone.

(1, 2) , (2) , (2) , (2) , (1) , (2) , (2) , (2)
1
2

Abstract

The histaminergic tuberomamillary nucleus (TMN) controls arousal and attention, and the firing of TMN neurons is state-dependent, active during waking, silent during sleep. Thyrotropin-releasing hormone (TRH) promotes arousal and combats sleepiness associated with narcolepsy. Single-cell reverse-transcription-PCR demonstrated variable expression of the two known TRH receptors in the majority of TMN neurons. TRH increased the firing rate of most (ca 70%) TMN neurons. This excitation was abolished by the TRH receptor antagonist chlordiazepoxide (CDZ; 50 mum). In the presence of tetrodotoxin (TTX), TRH depolarized TMN neurons without obvious change of their input resistance. This effect reversed at the potential typical for nonselective cation channels. The potassium channel blockers barium and cesium did not influence the TRH-induced depolarization. TRH effects were antagonized by inhibitors of the Na(+)/Ca(2+) exchanger, KB-R7943 and benzamil. The frequency of GABAergic spontaneous IPSCs was either increased (TTX-insensitive) or decreased [TTX-sensitive spontaneous IPSCs (sIPSCs)] by TRH, indicating a heterogeneous modulation of GABAergic inputs by TRH. Facilitation but not depression of sIPSC frequency by TRH was missing in the presence of the kappa-opioid receptor antagonist nor-binaltorphimine. Montirelin (TRH analog, 1 mg/kg, i.p.) induced waking in wild-type mice but not in histidine decarboxylase knock-out mice lacking histamine. Inhibition of histamine synthesis by (S)-alpha-fluoromethylhistidine blocked the arousal effect of montirelin in wild-type mice. We conclude that direct receptor-mediated excitation of rodent TMN neurons by TRH demands activation of nonselective cation channels as well as electrogenic Na(+)/Ca(2+) exchange. Our findings indicate a key role of the brain histamine system in TRH-induced arousal.
Fichier principal
Vignette du fichier
Parmentieretal2311_revertedHLH.pdf (202.94 Ko) Télécharger le fichier
Vignette du fichier
inserm-00387960_edited.pdf (711.43 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00387960 , version 1 (26-05-2009)

Identifiers

Cite

Régis Parmentier, Sergej Kolbaev, Boris P. Klyuch, David Vandael, Jian-Sheng Lin, et al.. Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone.. Journal of Neuroscience, 2009, 29 (14), pp.4471-83. ⟨10.1523/JNEUROSCI.2976-08.2009⟩. ⟨inserm-00387960⟩
419 View
1015 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More