The Role of Melanin-Concentrating Hormone in Repetitive Behavior

Melanin Concentrating Hormone (MCH) is a cyclic neuropeptide that has been evolutionarily conserved as an important sensory integrator. Over 60 years of literature suggests that it plays a central role in modulating a diverse set of behaviors which include feeding, stress, reward, reproduction and sleep in mammals. This broad regulation of functions is suggested by the wide distribution of its receptor, MCHR1, throughout the brain. However, little is known about what inputs directly regulate MCH neurons. Identifying these presynaptic inputs would provide a more nuanced and thorough understanding of the regulatory role of the MCH system. The work presented in this thesis aims to characterize the direct presynaptic inputs received by MCH neurons and identify the neurochemical composition of these regulatory inputs. We identified several brain nuclei that provide direct innervation to MCH neurons using rabies mediated circuit mapping technique in a cre-dependent MCH transgenic line. We further evaluated the neurochemical composition of the presynaptic cell population through immunofluorescent analysis. The second part of this work investigates the functional role of one of the identified presynaptic subpopulations, the oxytocin-MCH neural circuit. Using neuroanatomical, behavioral, and pharmacological tools we identify a novel role for the MCH system and a previously undefined neurocircuit by which oxytocin regulates repetitive behavior through the MCH system. The behavioral and anatomical findings reported in our study warrant further investigation of the role of this circuit in disorders symptomatic of perseverative behaviors