HcrtMCH Functional Interactions

Application of Hcrt results in an excitation of MCH neurons in slice preparations (where these neurons normally exhibit little spontaneous activity), depolarising membrane potential and increasing discharge frequency.76 Injection of Hcrt locally into the LHA also results in neuronal activation, determined as induction of expression of the immediate early gene c-Fos.85 Furthermore, adding Hcrt to hypothalamic cultures of pre-adult rats increases MCH expression in acute isolates but has the opposite effect in ten day-old cultures.56 These results suggest that in addition to more immediate effects on the electrical properties of the cell, local interactions within the LHA also involve long-term transcriptional changes. All in all, the predominant role of Hcrt in the regulation of MCH activity appears to be stimulatory. In contrast, MCH exerts inhibitory effects on LHA neurons.8687 While this appears to be a means for MCH neurons to regulate their own activity via inhibitory feedback,88 it has not yet been functionally demonstrated that MCH also can inhibit the activity specifically of Hcrt-expressing cells. As we learn more of the physiological role of the Hcrt and, in particular, MCH systems in sleep and arousal, the implications of these local interactions between the two LHA populations will likely become clearer.

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