title: Somatostatin triggers rhythmic electrical firing in hypothalamic GHRH neurons.
abstract: Hypothalamic growth hormone-releasing hormone (GHRH) neurons orchestrate body growth/maturation and have been implicated in feeding responses and ageing. However, the electrical patterns that dictate GHRH neuron functions have remained elusive. Since the inhibitory neuropeptide somatostatin (SST) is considered to be a primary oscillator of the GH axis, we examined its acute effects on GHRH neurons in brain slices from male and female GHRH-GFP mice. At the cellular level, SST irregularly suppressed GHRH neuron electrical activity, leading to slow oscillations at the population level. This resulted from an initial inhibitory action at the GHRH neuron level via K(+) channel activation, followed by a delayed, sst1/sst2 receptor-dependent unbalancing of glutamatergic and GABAergic synaptic inputs. The oscillation patterns induced by SST were sexually dimorphic, and could be explained by differential actions of SST on both GABAergic and glutamatergic currents. Thus, a tripartite neuronal circuit involving a fast hyperpolarization and a dual regulation of synaptic inputs appeared sufficient in pacing the activity of the GHRH neuronal population. These "feed-forward loops" may represent basic building blocks involved in the regulation of GHRH release and its downstream sexual specific functions.
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Osterstock
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Violeta
authors.initials: V
authors.lastname: Mitutsova
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Barre
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Granier
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontanaud
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Chazalon
authors.affiliation: Division of Molecular Neuroendocrinology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Carmignac
authors.affiliation: Division of Molecular Neuroendocrinology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
authors.forename: Iain C A F
authors.initials: IC
authors.lastname: Robinson
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.affiliation: Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
authors.affiliation: Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.|Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, United Kingdom.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, B15 2TH, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hodson
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
authors.affiliation: Inserm U-1191, Montpellier, France.|CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.|Université Montpellier, Montpellier, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Méry
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000037:antagonists & inhibitors; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D013004:Somatostatin / Q000502:physiology*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone