MOLECULAR PHARMACOLOGY, 50:230-235 (1996). ACCELERATED COMMUNICATION Leptin, the Obese Gene Product, Rapidly Modulates Synaptic Transmission in the Hypothalamus

We examined the effects of leptin, the product of the obese gene, on synaptic transmission in the arcuate nucleus in rat hypothalamic slices. Both leptin and neuropeptide Y (NPY) reduced the evoked glutamatergic excitatory postsynaptic cur-rent in the arcuate nucleus. NPY also depressed the GABAergic inhibitory postsynaptic current, although leptin had no effect. Leptin also decreased the input resistance of arcuate neurons, and this was accompanied by the activation of an outward current at depolarized potentials. Leptin modulated Ca2 sig-nals in acutely isolated arcuate neurons. In some cells, the intracellular calcium concentration rise produced by 50 m K was decreased, whereas in others it was increased. However, leptin produced no effects on synaptic transmission and little or no effect on Ca2 signaling in the hypothalamus of Zucker fatty rats that contain mutated Ieptin receptors. On the other hand