Cellular mechanisms of thermosensing in orexin neurons

Belanger-Willoughby, Natasha (2013) Cellular mechanisms of thermosensing in orexin neurons. Masters thesis, Memorial University of Newfoundland.

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Abstract

Hypothalamic orexin neurons promote energy intake and expenditure. Thus, satiety and behavioural inactivity that accompany post-prandial rises in body temperature may, in part, be explained by the inhibition of orexin neurons. Using whole-cell patch clamp on rat brain slices, I investigated cellular mechanisms of orexin thermosensing. Orexin neurons are inhibited by elevated temperatures in-vitro but neighboring melanin-concentrating hormone neurons are not temperature-sensitive. Orexin neuronal inhibition is mediated by A TP-sensitive potassium channels, which are modulated by the UCP2 inhibitor genipin. Warming additionally revealed an increase in glutamatergic transmission (mEPSCs). This effect was attenuated by the transient receptor potential vanilloid-1 (TRPV 1) channel inhibitor AMG9810, suggesting mediation by pre- and post-synaptic TRPV 1 channels. Orexin neurons in rats overfed with high-fat westerndiet had impaired thermosensing mechanisms. In conclusion, this study suggests that postprandial thermogenesis inhibits orexin neurons to promote satiety and lethargic behaviours and additionally implicates a role for orexin thermosensing in diet-induced overconsumption.

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