| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROSCIENCE |
1 Neuroscience Program
2 Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
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 µM) 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.
(Received 27 January 2005;
accepted after revision 27 March 2006;
first published online 31 March 2006)
Corresponding author B. N. Smith: Department of Cell and Molecular Biology, Tulane University, 6400 Freret Street, New Orleans, LA 70118, USA. Email: bnsmith{at}tulane.edu
This article has been cited by other articles:
|
|
 |
|
  T. W. Bailey, S. M. Appleyard, Y.-H. Jin, and M. C. Andresen Organization and Properties of GABAergic Neurons in Solitary Tract Nucleus (NTS) J Neurophysiol, April 1, 2008; 99(4): 1712 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Peters, S. M. Simasko, and R. C. Ritter Leptin Analog Antagonizes Leptin Effects on Food Intake and Body Weight but Mimics Leptin-Induced Vagal Afferent Activation Endocrinology, June 1, 2007; 148(6): 2878 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-L. Li, L.-C. Chiou, Y. S. Lin, J.-R. Hsieh, and L.-L. Hwang Electrophysiological study on the effects of leptin in rat dorsal motor nucleus of the vagus Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2136 - R2143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Huo, L. Maeng, C. Bjorbaek, and H. J. Grill Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin Endocrinology, May 1, 2007; 148(5): 2189 - 2197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Williams, A. Zsombok, and B. N. Smith Rapid Inhibition of Neurons in the Dorsal Motor Nucleus of the Vagus by Leptin Endocrinology, April 1, 2007; 148(4): 1868 - 1881. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
