Journal article
Thyrotropin-releasing hormone increases behavioral arousal through modulation of hypocretin/orexin neurons
The Journal of neuroscience, Vol.29(12), pp.3705-3714
03/25/2009
Handle:
https://hdl.handle.net/2376/108011
PMCID: PMC2712668
PMID: 19321767
Abstract
Thyrotropin-releasing hormone (TRH) has previously been shown to promote wakefulness and to induce arousal from hibernation. Expression of TRH-R1 (TRH receptor 1) is enriched in the tuberal and lateral hypothalamic area (LHA), brain regions in which the hypocretin/orexin (Hcrt) cells are located. Because the Hcrt system is implicated in sleep/wake control, we hypothesized that TRH provides modulatory input to the Hcrt cells. In vitro electrophysiological studies showed that bath application of TRH caused concentration-dependent membrane depolarization, decreased input resistance, and increased firing rate of identified Hcrt neurons. In the presence of tetrodotoxin, TRH induced inward currents that were associated with a decrease in frequency, but not amplitude, of miniature postsynaptic currents (PSCs). Ion substitution experiments suggested that the TRH-induced inward current was mediated in part by Ca(2+) influx. Although TRH did not significantly alter either the frequency or amplitude of spontaneous excitatory PSCs, TRH (100 nm) increased the frequency of spontaneous inhibitory PSCs by twofold without affecting the amplitude of these events, indicating increased presynaptic GABA release onto Hcrt neurons. In contrast, TRH significantly reduced the frequency, but not amplitude, of miniature excitatory PSCs without affecting miniature inhibitory PSC frequency or amplitude, indicating that TRH also reduces the probability of glutamate release onto Hcrt neurons. When injected into the LHA, TRH increased locomotor activity in wild-type mice but not in orexin/ataxin-3 mice in which the Hcrt neurons degenerate postnatally. Together, these results are consistent with the hypothesis that TRH modulates behavioral arousal, in part, through the Hcrt system.
Metrics
5 Record Views
Details
- Title
- Thyrotropin-releasing hormone increases behavioral arousal through modulation of hypocretin/orexin neurons
- Creators
- Junko Hara - Biosciences Division, SRI International, Menlo Park, California 94025, USADmitry GerashchenkoJonathan P WisorTakeshi SakuraiXinmin XieThomas S Kilduff
- Publication Details
- The Journal of neuroscience, Vol.29(12), pp.3705-3714
- Academic Unit
- Biomedical Sciences, Department of
- Publisher
- United States
- Grant note
- R01 MH061755 / NIMH NIH HHS R01MH061755 / NIMH NIH HHS R01 MH078194-01A2 / NIMH NIH HHS R01 AG020584-04 / NIA NIH HHS R01 MH061755-09 / NIMH NIH HHS R01AG020584 / NIA NIH HHS R01 AG020584 / NIA NIH HHS R01 MH061755-07 / NIMH NIH HHS R01 MH061755-08 / NIMH NIH HHS R01 AG020584-05 / NIA NIH HHS R01 AG020584-03 / NIA NIH HHS R01MH078194 / NIMH NIH HHS R01 MH078194 / NIMH NIH HHS
- Identifiers
- 99900547028601842
- Language
- English
- Resource Type
- Journal article