Characterization of diverse excitatory currents in Melanin-Concentrating hormone neurons

Abstract

Positive energy balance and sleep are coordinated by a lateral hypothalamic neuronal subpopulation known as Melanin concentrating hormone (MCH) neurons. The excitatory transmitter glutamate plays an important role in shaping the activity of MCH neurons, which is regulated by glutamate transporters present on astrocytes and neurons. Here, we aimed to investigate the role of controlling excitatory signaling via glutamatergic receptors in MCH neurons. We performed in vitro electrophysiological (Whole-cell patch clamp) recordings from acute brain slices to investigate the effect of ambient glutamate by using a glutamate transporter blocker. We identified and characterized three kinetically diverse excitatory currents in addition to excitatory postsynaptic currents (EPSCs): tonic inward current (TIC), step currents and slow inward currents (SICs). TIC had the longest time course and amplitude followed by the step currents and SICs. These currents are mediated by glutamatergic (non-NMDA and NMDA) receptors and dependent on the action potential-dependent exocytotic release. 12 h fasting reduced the amplitude and frequency of TIC and SICs respectively, suggesting that ambient-glutamate regulation by glutamate transporter is altered under homeostatic challenge, therefore the excitability of MCH neurons. Taken together, MCH neurons are under the influence of ambient glutamate modulated by glutamate transporters. This could possibly have physiological implications in energy homeostasis.