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Orexin-A and ghrelin depolarize the same pedunculopontine tegmental neurons in rats: an in vitro study
Juhyon Kim1, Kazuki Nakajima, Yutaka Oomura
1Division of Bio-Information Engineering, Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
Abstract:
Orexin (ORX), also called hypocretin, and ghrelin are newly identified peptides in the brain and/or peripheral organs, and they are involved in the regulation of sleep-wakefulness as well as feeding. In our previous studies we have found that ORX and ghrelin each depolarizes more than half of the cholinergic neurons recorded in the pedunculopontine tegmental nucleus (PPT) via a dual ionic mechanism including a decrease of K(+) conductance and an increase of nonselective cationic conductance. Thus, the present study was carried out to investigate whether ORX-A and ghrelin both depolarize the same PPT neuron. About 60% of PPT neurons examined was depolarized by both ORX-A and ghrelin, 20% by ORX-A alone, and 10% by ghrelin alone. The remaining 10% did not respond to these peptides. In neurons which were responsive to both ORX-A and ghrelin, the depolarizations induced by ORX-A and ghrelin were additive. In addition, the ORX-A- and ghrelin-induced depolarizations were both blocked by D609, a phosphatidylcholine-specific phospholipase C (PLC) inhibitor. These results suggest that same PPT neurons with receptors for ORX and ghrelin are involved in the cellular process through which ORX and ghrelin participate in the regulation of sleep wakefulness, and that the excitatory effects of ORX and ghrelin on PPT neurons are mediated by PLC.
Insights
Orexin (ORX) and ghrelin both excite the same brainstem neurons that regulate sleep-wake cycles. This dual action is mediated by a shared signaling pathway involving phospholipase C (PLC).
Area of Science:
- Neuroscience
- Neuroendocrinology
Background:
- Orexin (ORX), also known as hypocretin, and ghrelin are key peptides regulating sleep-wakefulness and feeding behaviors.
- Previous research indicated that both ORX and ghrelin can depolarize cholinergic neurons in the pedunculopontine tegmental nucleus (PPT).
Purpose of the Study:
- To determine if ORX-A and ghrelin act on the same PPT neurons.
- To investigate the ionic mechanisms and signaling pathways underlying the effects of ORX-A and ghrelin on PPT neurons.
Main Methods:
- Electrophysiological recordings were performed on PPT neurons.
- Neurons were exposed to ORX-A and ghrelin to assess their responses.
- The effects of D609, a phospholipase C (PLC) inhibitor, were examined.
Main Results:
- Approximately 60% of PPT neurons responded to both ORX-A and ghrelin, exhibiting additive depolarizations.
- 20% of neurons responded only to ORX-A, and 10% only to ghrelin.
- The depolarizing effects of both peptides were blocked by the PLC inhibitor D609.
Conclusions:
- Specific PPT neurons possess receptors for both ORX and ghrelin, suggesting a convergence of these systems.
- The findings indicate that ORX and ghrelin utilize a common PLC-mediated pathway to excite PPT neurons.
- This shared mechanism highlights the integrated role of ORX and ghrelin in regulating sleep-wakefulness via PPT neuronal activity.
