In summary, our recent studies indicate that Hcrt/Orx peptides excite mesopontine cholinergic and non-cholinergic neurons of the LDT via multiple actions that are likely to have a powerful impact on their activity and integrative properties. Application of Hcrt/Orx causes sufficient depolarization of LDT neurons to drive even quiescent neurons into repetitive firing. This drive is mediated, at least partly, by activation of a noisy cation current and by excitation of presynaptic glutamate-releasing afferents. In contrast, Hcrt/Orx effects on presynaptic inhibitory afferents were more diverse. This may reflect a less important influence of Hcrt/Orx on inhibitory inputs or, more likely, may indicate that subpopulations of LDT neurons are differentially regulated by Hcrt/Orx.

Hcrt/Orx also produces a long-lasting increase in intracellular calcium in LDT neurons that arises from a calcium influx, mediated in part through L-type calcium channels rather than by release from intracellular stores or through reverse operation of the Na+/Ca2+ exchanger. Based on simultaneous whole-cell recording and calcium imaging, the cation current appears to contribute surprisingly little to the Hcrt/Orx-evoked calcium influx. Rather, it appears the cation current provides the depolarizing drive necessary to activate voltage-operated calcium-permeable channels, including L-type channels. These calcium channels, themselves appear to be up-modulated by Hcrt/Orx, perhaps through activation of PKC.45

Was this article helpful?

0 0
Natural Cures For Insomnia

Natural Cures For Insomnia

How Would You Love To Finally Get A Decent Night's Sleep? Do you toss and turn all night long without getting much of a wink of sleep? Are you tired of counting sheep for hours without falling asleep? Wouldn't you love to be able to fall asleep simply, easily and naturally, without pills, potions or harmful medicine?

Get My Free Ebook

Post a comment