The Journal of Neuroscience, February 14, 2007, 27(7):1631-1641; doi:10.1523/JNEUROSCI.2693-06.2007
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Cellular/Molecular
Dual-Level Afferent Control of Growth Hormone-Releasing Hormone (GHRH) Neurons in GHRHGreen Fluorescent Protein Transgenic Mice
Nelly Baccam,1
Gérard Alonso,1
Thomas Costecalde,1
Pierre Fontanaud,1
François Molino,1
Iain C. A. F. Robinson,2
Patrice Mollard,1 and
Pierre-François Méry1
1Département d'Endocrinologie, Institut de Génomique Fonctionnelle, Institut National de la Santé et de la Recherche Scientifique U661, Centre National de la Recherche Scientifique UMR 5203, Université Montpellier 1, Université Montpellier 2, 34094 Montpellier, France, and 2Division of Molecular Neuroendocrinology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
Correspondence should be addressed to Pierre-François Méry, Département d'Endocrinologie, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier Cedex 5, France. Email: pierre-francois.mery{at}igf.cnrs.fr
The organization of the peptidergic neurons of the hypothalamic arcuate nucleus is not fully understood. These include growth hormone-releasing hormone (GHRH) neurons involved in growth and metabolism. We studied identified GHRH neurons of GHRHgreen fluorescent protein transgenic mice using patch-clamp methods and focused on gender differences, which govern the physiological patterns of GHRH release. Both the spontaneous firing rates and the intrinsic properties of GHRH neurons were similar in males and females, although higher glutamatergic currents were noticed in females. Surprisingly, marked gender differences in GHRH neuronal activity were observed in response to the muscarinic agonist carbachol (CCh). In females, CCh enhanced action potential firing in all GHRH neurons. In males, CCh enhanced action potential firing in two-thirds of GHRH neurons, whereas it decreased firing in the remainders. M1 agonist McN-A343 (10 µM) mimicked, and M1 antagonist pirenzepine (3 µM) blocked the effects of CCh. In both genders, CCh did not change the intrinsic properties of GHRH neurons, although it strongly increased the frequency of glutamatergic currents, in the presence or absence of tetrodotoxin. In males only, CCh enhanced the frequency of GABAergic currents, and this modulation was antagonized by tetrodotoxin. Thus, the muscarinic regulation involved differential control of afferent inputs at short and long distances in male and female mice. The dual-level control could be a mechanism whereby the selective modulation of the GHRH system (short-distance control) is adjusted to the integrated regulation of arcuate nucleus activity (long-distance control).
Key words: acetylcholine; action potential; GABA; glutamate; patch clamp; growth hormone
Received Nov. 30, 2005;
revised Nov. 21, 2006;
accepted Dec. 31, 2006.
Correspondence should be addressed to Pierre-François Méry, Département d'Endocrinologie, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier Cedex 5, France. Email: pierre-francois.mery{at}igf.cnrs.fr
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