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

• Published in: Neuroscience 2009-03, Vol.159 (1), p.83-93
• Main Authors: Hisadome, K, Smith, M.A, Choudhury, A.I, Claret, M, Withers, D.J, Ashford, M.L.J
• Format: Article
• Language: English
• Subjects: 5-HT; 5-HT1F receptor; Action Potentials - drug effects; Agouti-Related Protein - genetics; Agouti-Related Protein - metabolism; Animals; Arcuate Nucleus of Hypothalamus - cytology; Arcuate Nucleus of Hypothalamus - metabolism; Biological and medical sciences; Biophysical Phenomena - drug effects; Cellular Neuroscience; Electric Stimulation - methods; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins - genetics; hypothalamus; In Vitro Techniques; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Integrases - genetics; Integrases - metabolism; K+ channel; Mice; Mice, Transgenic; Neural Inhibition - drug effects; Neurology; Neurons - drug effects; Neurons - physiology; Neuropeptide Y - genetics; Patch-Clamp Techniques - methods; POMC; Potassium Channel Blockers - pharmacology; Potassium Channels - physiology; Pro-Opiomelanocortin - genetics; Pro-Opiomelanocortin - metabolism; Rats; RIPCre; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.12.003

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.