Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin

TLDR

Leptin, a fat‑derived hormone, regulates energy balance by modulating neuropeptide Y and proopiomelanocortin neuron activity in the hypothalamic arcuate nucleus. The study aimed to investigate how leptin influences the intrinsic activity of these neurons. To do so, the authors generated mice expressing distinct green fluorescent proteins in each neuronal type to monitor their activity and leptin responses. Leptin‑deficient mice exhibited altered excitatory and inhibitory synapse numbers and postsynaptic currents on these neurons, but systemic leptin delivery rapidly restored synaptic density within six hours—well before changes in food intake—suggesting leptin‑mediated plasticity may underlie its behavioral effects.

Abstract

The fat-derived hormone leptin regulates energy balance in part by modulating the activity of neuropeptide Y and proopiomelanocortin neurons in the hypothalamic arcuate nucleus. To study the intrinsic activity of these neurons and their responses to leptin, we generated mice that express distinct green fluorescent proteins in these two neuronal types. Leptin-deficient (ob/ob) mice differed from wild-type mice in the numbers of excitatory and inhibitory synapses and postsynaptic currents onto neuropeptide Y and proopiomelanocortin neurons. When leptin was delivered systemically to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. These data suggest that leptin-mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects.