Rapid inhibition of neural excitability in the rat dorsal vagal complex by leptin: Implications for ingestive behaviour
Description
The fat-derived hormone leptin communicates the status of energy stores to the brain and data suggests that the leptin pathway plays an important role in body weight control. Since leptin's discovery, leptin effects in the hypothalamus have been emphasized, whereas leptin effects on other central autonomic regions like the brainstem have been understudied. Recent studies implicate a role for the dorsal vagal complex in the feeding modulation attributed to leptin. However, possible direct cellular effects of leptin within the vagal complex have never been studied. These experiments were aimed at testing the hypothesis that at least part of the distributed network of leptin responsive cells resides within the DVC and identifying the synaptic and cellular modulation of neurons within the DVC by leptin Leptin caused a membrane hyperpolarization of gastric-related DVC neurons and was accompanied by a decrease in whole-cell input resistance and responsiveness. The leptin-induced hyperpolarization exhibited a dependence of membrane potential and was blocked by a sulfonylurea and wortmannin, which in all implicates activation of an ATP-sensitive K+ channel via a P13-kinase mechanism. The data presented here support a role for leptin in both suppression of excitatory synaptic inputs and a direct cellular inhibition of the neurons in the DVC, which are critical modulators of gastric function. Due to leptin's effects in the DVC and in particular gastric-related neurons, these responses can now be associated with neurons involved in the process of feeding and ingestion. Leptin's rapid effects may report a feed-back response to changing leptin during varying energy needs. The cellular inhibition of the DVC by leptin may also describe a modulation of several homeostatic modalities within the autonomic nervous system