5-ht inhibition of rat insulin 2 promoter cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus

K. Hisadome, M. A. Smith, A. I. Choudhury, M. Claret, D. J. Withers, M. L. J. Ashford

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    Abstract

    A number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT1F receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT1F receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)83-93
    Number of pages11
    JournalNeuroscience
    Volume159
    Issue number1
    DOIs
    Publication statusPublished - 3 Mar 2009

    Keywords

    • 5-HT
    • hypothalamus
    • K+ channel
    • RIPCre
    • POMC
    • 5-HT1F receptor
    • MELANOCYTE-STIMULATING HORMONE
    • CENTRAL MELANOCORTIN SYSTEM
    • ENERGY HOMEOSTASIS
    • RECEPTOR AGONIST
    • FOOD-INTAKE
    • SIGNAL-TRANSDUCTION
    • MOLECULAR-CLONING
    • NEUROPEPTIDE-Y
    • POMC NEURONS
    • SEROTONIN

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