A Cellular Mechanism of Leptin Mediated Responses in Mouse NTS Neurons

Abstract

The nucleus of the solitary tract (NTS) in the medulla is the site of first synapse for sensory afferents of the vagal and glosspharyngeal nerves. A dense termination of sensory input reflects a key function of the NTS as an integrative center for a number of vitally important homeostatic reflexes such as cardiovascular, respiratory and visceral reflexes. Little is known concerning the cellular rules of information integration in the NTS, especially how the metabolic state influences respiratory output. Leptin is an anorexigenic cytokine acting through activation of specific G‐protein‐coupled receptors (GPCRs). Leptin receptors are expressed in the NTS, but the mechanism of action following their activation remains unclear. Moreover, the precise identity of the cells expressing the leptin receptor in the NTS is also elusive.Our study has two main goals: 1‐ to uncover the expression of individual genes that identify neuronal subpopulations of cells expressing the leptin receptor; and 2‐ to identify the ion channel(s) mediating the action of leptin in these different cellular populations. To pursue these goals we combine genetic tagging of leptin receptor expressing neurons, electrophysiological recordings and single cell RT‐PCR to test the expression of candidate channels and neuropeptides. Our data show that NTS leptin receptor expressing neurons belong to two distinct populations characterized by different firing patterns (bursting vs. regular firing). Further, we found that leptin receptor activation leads to membrane depolarization that is mediated by a cationic conductance. This mechanism appears to be the same in both the cell populations. The PCR data suggest that the conductance activated by leptin is, at least in part, mediated by NALCN channels.Support or Funding InformationThis study was supported by NIH grant HL122921