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

doi:10.1016/j.neuroscience.2008.12.003

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

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

253 Downloads (Pure)

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 language	English
Pages (from-to)	83-93
Number of pages	11
Journal	Neuroscience
Volume	159
Issue number	1
DOIs	https://doi.org/10.1016/j.neuroscience.2008.12.003
Publication status	Published - 3 Mar 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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10.1016/j.neuroscience.2008.12.003

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http://ukpmc.ac.uk/articles/PMC2661429

Cite this

@article{65e45f4f51c5479c8fdfc62b4115854d,

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

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.",

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",

author = "K. Hisadome and Smith, \{M. A.\} and Choudhury, \{A. I.\} and M. Claret and Withers, \{D. J.\} and Ashford, \{M. L. J.\}",

year = "2009",

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doi = "10.1016/j.neuroscience.2008.12.003",

language = "English",

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TY - JOUR

T1 - 5-ht inhibition of rat insulin 2 promoter cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus

AU - Hisadome, K.

AU - Smith, M. A.

AU - Choudhury, A. I.

AU - Claret, M.

AU - Withers, D. J.

AU - Ashford, M. L. J.

PY - 2009/3/3

Y1 - 2009/3/3

N2 - 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.

AB - 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.

KW - 5-HT

KW - hypothalamus

KW - K+ channel

KW - RIPCre

KW - POMC

KW - 5-HT1F receptor

KW - MELANOCYTE-STIMULATING HORMONE

KW - CENTRAL MELANOCORTIN SYSTEM

KW - ENERGY HOMEOSTASIS

KW - RECEPTOR AGONIST

KW - FOOD-INTAKE

KW - SIGNAL-TRANSDUCTION

KW - MOLECULAR-CLONING

KW - NEUROPEPTIDE-Y

KW - POMC NEURONS

KW - SEROTONIN

U2 - 10.1016/j.neuroscience.2008.12.003

DO - 10.1016/j.neuroscience.2008.12.003

M3 - Article

C2 - 19135134

SN - 0306-4522

VL - 159

SP - 83

EP - 93

JO - Neuroscience

JF - Neuroscience

IS - 1

ER -

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

Abstract

UN SDGs

Keywords

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