Melanin-concentrating hormone mediated inhibition of lateral septum neurons

Abstract

Melanin-concentrating hormone (MCH) is produced in the lateral hypothalamus. It has important roles in homeostatic and motivated behaviour. As MCH projections and receptors are widely distributed, the brain regions underlying MCH functions are not well understood. We showed that MCH neurons send dense projections to the lateral septum (LS) and innervate LS neurons by glutamate release. Consistently, retrograde injections into the LS showed that MCH neurons that innervate the LS are largely distributed medial to the fornix. However, it is not known if MCH can regulate the activity of LS neurons. In order to characterize MCH action in the LS, we first mapped the distribution of MCH-immunoreactive fibers and MCH receptor mRNA (Mchr1) throughout the LS. We observed the highest expression of both MCH fibers and Mchr1 toward the lateral and ventral borders of the intermediate subregion of the LS, and we selected LS cells for whole-cell patch clamp recordings from these regions. Bath application of MCH directly hyperpolarized LS neurons and elicited a membrane current that reversed at the equilibrium potential for chloride ions. This MCH-mediated hyperpolarization and current were blocked by the GABAA receptor antagonist bicuculline and indicated that GABAA-dependent mechanisms underlie the inhibitory actions of MCH in the LS. By contrast, MCH does not alter the frequency of glutamatergic or GABAergic input to LS neurons. In aggregate, the postsynaptic actions of MCH in the LS suggests that in addition to glutamate, MCH neurons may also regulate the LS by MCH release.