LEPTIN DEPOLARIZES RAT HYPOTHALAMIC PARAVENTRICULAR NUCLEUS NEURONS

Leptin, the protein product of the ob/ob gene, is thought to have a ce ntral site of action, presumably within the hypothalamus, through whic h it regulates feeding behavior. The paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direc t membrane effects of leptin on neurons in a coronal PVN slice. Bath a pplication of the physiologically active leptin fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the type I cell s tested (n = 17) and 67% of the type II cells tested (n = 9). By cont rast, the physiologically inactive leptin fragment (amino acids 57-92) had no discernible effect on membrane potential (n = 7). The effects of this peptide were unaffected following synaptic isolation of the ce lls by bath application of the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six cells demonstrated that leptin i ncreased a nonspecific cation conductance with a reversal potential ne ar -30 mV. These findings suggest that neurons in PVN may play an impo rtant role in the central neuronal circuitry involved in the physiolog ical response to leptin.