Leptin directly regulate intrinsic neuronal excitability in hypothalamic POMC neurons but not in AgRP neurons in food restricted mice.

Leptin plays a pivotal role in the central control of energy balance through leptin receptors expressed on specific hypothalamic nuclei. Leptin suppresses food intake and body weight and ameliorates hyperglycemia by acting on the AgRP and POMC neurons of the arcuate nucleus. Leptin action on POMC neurons are essential for control of body weight and blood glucose levels and are known to be mediated by JAK-STAT3 and PI3K signalling pathway thus increase POMC mRNA and intrinsic excitability. The effects of leptin on AgRP neurons are not as clear although it has been reported to hyperpolarize AgRP neurons through change of K conductance. Using cell-attached patch and whole cell patch configuration, we directly assessed neuronal response to leptin in GFP labelled AgRP or POMC neurons in mice after 18 h of food deprivation. We found leptin has a direct effect on POMC neuron through increased intrinsic excitability and decreased inhibitory synaptic inputs. However, leptin does not have any effect on intrinsic excitability of AgRP neurons in fasted condition although food deprivation induced increase of firing frequency of AgRP neurons. In conclusion, leptin probably has a direct and acute effect on POMC neurons but not on AgRP neurons to control their excitability within feeding-regulatory neuronal circuitry.