Rapid inhibition of neural excitability in the nucleus tractus solitarii by leptin: implications for ingestive behaviour
- 31 May 2006
- journal article
- research article
- Published by Wiley in The Journal of Physiology
- Vol. 573 (2), 395-412
- https://doi.org/10.1113/jphysiol.2006.106336
Abstract
The fat-derived peptide leptin regulates cellular activity in areas of the CNS related to feeding, and application of leptin to the fourth ventricle or the nucleus tractus solitarii (NTS) inhibits food intake and weight gain. The hypothesis that leptin modulates cellular activity in the NTS was tested using whole-cell patch-clamp recordings in brainstem slices. Leptin caused a rapid membrane hyperpolarization in 58% of rat NTS neurones, including neurones receiving tractus solitarius input (i.e. viscerosensory) and those involved in regulating output to the stomach, identified after gastric inoculation with a transneuronal retrograde viral label. The hyperpolarization was accompanied by a decrease in input resistance and cellular responsiveness, reversed near the K(+) equilibrium potential, and was prevented by intracellular Cs(+). Perfusion of tolbutamide (200 microm) or wortmannin (100-200 nm) prevented the hyperpolarization, indicating activation of an ATP-sensitive K(+) channel via a PI3 kinase-dependent mechanism. Constant latency tractus solitarius-evoked EPSCs were decreased in amplitude by leptin, and the paired-pulse ratio was increased, suggesting effects on evoked EPSCs involved activation of receptors on vagal afferent terminals. Leptin reduced the frequency of spontaneous and miniature EPSCs, whereas IPSCs were largely unaffected. Leptin's effects were observed in neurones from lean, but not obese, Zucker rats. Neurones that expressed enhanced green fluorescent protein (EGFP) in a subpopulation of putative GABAergic neurones in transgenic mice did not respond to leptin, whereas unlabelled murine neurones responded similarly to rat neurones. Leptin therefore directly and rapidly suppresses activity of excitatory NTS neurones likely to be involved in viscerosensory integration and/or premotor control of the stomach.Keywords
This publication has 66 references indexed in Scilit:
- Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasisJournal of Comparative Neurology, 2005
- Modulation of Synaptic Transmission in the Rat Nucleus of the Solitary Tract by Endomorphin-1Journal of Neurophysiology, 2005
- Purinergic and Vanilloid Receptor Activation Releases Glutamate from Separate Cranial Afferent Terminals in Nucleus Tractus SolitariusJournal of Neuroscience, 2004
- Glucosensing neurons do more than just sense glucoseInternational Journal of Obesity, 2001
- Chemical characterization of leptin-activated neurons in the rat brainJournal of Comparative Neurology, 2000
- Essential Role of Phosphoinositide 3-Kinase in Leptin-inducedK ATP Channel Activation in the Rat CRI-G1 Insulinoma Cell LineJournal of Biological Chemistry, 2000
- Intraventricular Leptin Reduces Food Intake and Body Weight of Lean Rats but Not Obese Zucker RatsHormone and Metabolic Research, 1996
- Transient increase in obese gene expression after food intake or insulin administrationNature, 1995
- Central connections of the sensory and motor nuclei of the vagus nerveJournal of the Autonomic Nervous System, 1983
- Brainstem projections of sensory and motor components of the vagus nerve in the ratJournal of Comparative Neurology, 1982