Leptin Inhibits Presympathetic Neurons in the Rostral Ventrolateral Medulla

Abstract

Leptin is greatly involved in the regulation of food intake, and dysfunction of leptin or its receptors is associated with obesity. Numerous evidence indicate that obesity is linked to increased prevalence of hypertension. The sympathetic nervous system (SNS) is greatly involved in the regulation of arterial blood pressure and neurons in the rostral ventrolateral medulla (RVLM) are critical components of both the SNS and cardiovascular regulation. In this study we used whole-cell patch-clamp recordings from presympathetic kidney-related RVLM neurons identified with retrograde viral labeling and tested the hypothesis that leptin reduces neuronal excitability of RVLM neurons. Application of leptin (500 nM) caused a rapid membrane hyperpolarization (3.7 ± 1.4 mV change) in half of the recorded presympathetic RVLM neurons without affecting the rest of the recorded cells. The hyperpolarization was accompanied with an increase of input resistance from 287 ± 95 MΩ to 336 ± 97 MΩ. In addition, leptin decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSC) by 35.6 ± 0.1% without changing sEPSC amplitude. In contrast, leptin did not alter the inhibitory neurotransmission. In summary, our data demonstrate that leptin reduces the excitability of a subset of presympathetic RVLM neurons via pre- and postsynaptic mechanisms and suggest a potential control mechanism of SNS activity. Supported by Tulane University COBRE in Hypertension (NIH P30GM103337).