Electrophysiological effects of MCH on neurons in the hypothalamus

Abstract

Melanin concentrating hormone (MCH) has been implicated in many brain functions and behaviors essential to the survival of animals. The hypothalamus is one of the primary targets where MCH-containing nerve fibers and MCH receptors are extensively expressed and its actions in the brain are exerted. Since the identification of MCH receptors as orphan G protein coupled receptors, the cellular effects of MCH have been revealed in many non-neuronal expression systems (including Xenopus oocytes and cell lines), however, the mechanism by which MCH modulates the activity in the neuronal circuitry of the brain is still under investigation. This review summarizes our current knowledge of electrophysiological effects of MCH on neurons in the hypothalamus, particularly in the lateral hypothalamus. Generally, MCH exerts inhibitory effects on neurons in this structure and may serve as a homeostatic regulator in the lateral hypothalamic area. Given the contrast between the limited data on cellular functions of MCH in the hypothalamus versus a fast growing body of evidence on the vital role of MCH in animal behavior, further investigations of the former are warranted.

Fig. 1. Schematic representation of localization of hypocretin/orexin (Hcrt)- and MCH-containing neurons in the LH

Cell bodies of hypocretin/orexin- (blue dots) and MCH-containing (red dots) neurons are mainly localized in the perifornical-lateral hypothalamic area. These two groups of neurons intermingle but do not overlap. Reciprocal synaptic innervations between hypocretin/orexin and MCH neurons are reported as shown in the box. Synaptic contacts among hypocretin/orexin neurons (solid blue boutons on hypocretin/orexin neurons) and among MCH neurons (broken red boutons on MCH neurons) have been reported. Abbreviations: 3V, the third ventricle; PVN, periventricular nucleus; ARC, arcuate nucleus; DMH, dorsomedial hypothalamus; VMH, ventromedial hypothalamus; LH, lateral hypothalamus; f, fornix.

Fig. 2. Schematic illustration of the interaction between hypocretin/orexin (HCRT) and MCH neurons in the LH

Hypocretin/orexin acts as the major excitatory force in the LH since it may increase excitation in both the hypocretin/orexin and MCH neurons, while MCH works as a feedback regulator. A, under resting conditions, MCH does not inhibit (dashed line) baseline action potential generation and synaptic transmission in hypocretin/orexin neurons (solid line), which may permit the easy activation of hypocretin/orexin neurons. B, intensive activity in hypocretin/orexin neurons resulting from stimulatory inputs leads to an excitatory effect of hypocretin/orexin on MCH neurons (solid line). C, MCH exerts its inhibitory effects on hypocretin/orexin neurons when the excitation of the hypocretin/orexin system reaches a certain level (solid line), thus fine-tuning the final output of the hypocretin/orexin neurons (solid line). It is hypothesized that MCH may work as a homeostatic regulator in such a system of “checks and balances” to maintain the excitability necessary for the brain to function and to prevent over-excitation that might compromise delicately controlled behaviors.