5-HT inhibition of rat insulin 2 promoter Cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus.
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-HT(1F) receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT(1F) 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.
Hisadome
K
K
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
Smith
M A
MA
Choudhury
A I
AI
Claret
M
M
Withers
D J
DJ
Ashford
M L J
ML
D000200:Action Potentials / Q000187:drug effects; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000378:metabolism; D055592:Biophysical Phenomena / Q000187:drug effects; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D054369:Agouti-Related Protein; D055504:Insulin Receptor Substrate Proteins; D009478:Neuropeptide Y; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012702:Serotonin Antagonists; D049452:Green Fluorescent Proteins; D012701:Serotonin; D011333:Pro-Opiomelanocortin; C045073:Cre recombinase; D019426:Integrases