Mechanisms of neuropeptide Y, peptide YY, and pancreatic polypeptide inhibition of identified green fluorescent protein-expressing GABA neurons in the hypothalamic neuroendocrine arcuate nucleus

被引:100
作者
Acuna-Goycolea, C
Tamamaki, N
Yanagawa, Y
Obata, K
van den Pol, AN
机构
[1] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA
[2] Kumamoto Univ, Dept Morphol Neural Sci, Kumamoto 8608556, Japan
[3] Gunma Univ, Dept Genet & Behav Neurosci, Maebashi, Gumma 3718511, Japan
[4] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Kawaguchi 3320012, Japan
[5] Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Kawaguchi 3320012, Japan
[6] RIKEN, Brain Sci Inst, Obata Res Unit, Wako, Saitama 3510198, Japan
关键词
neuroendocrine; glutamate; GABA; mediobasal hypothalamus; feeding; neuropeptide Y;
D O I
10.1523/JNEUROSCI.1008-05.2005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The fast inhibitory transmitter GABA is robustly expressed in the arcuate nucleus (ARC) and appears to play a major role in hypothalamic regulation of endocrine function and energy homeostasis. Previously, it has not been possible to record selectively from GABA cells, because they have no defining morphological or physiological characteristics. Using transgenic mice that selectively express GFP (green fluorescent protein) in GAD67 (glutamic acid decarboxylase 67)-synthesizing cells, we identified ARC GABA neurons (n > 300) and used whole-cell recording to study their physiological response to neuropeptide Y (NPY), the related peptide YY3-36(PYY3-36), and pancreatic polypeptide (PP), important modulators of ARC function. In contrast to other identified ARC cells in which NPY receptor agonists were reported to generate excitatory actions, we found that NPY consistently reduced the firing rate and hyperpolarized GABA neurons including neuroendocrine GABA neurons identified by antidromic median eminence stimulation. The inhibitory NPY actions were mediated by postsynaptic activation of G-protein-linked inwardly rectifying potassium (GIRK) and depression of voltage-gated calcium currents via Y-1 and Y-2 receptor subtypes. Additionally, NPY reduced spontaneous and evoked synaptic glutamate release onto GABA neurons by activation of Y-1 and Y-5 receptors. The peptide PYY3-36, a peripheral endocrine signal that can act in the brain, also inhibited GABA neurons, including identified neuroendocrine cells, by activating GIRK conductances and depressing calcium currents. The endogenous Y-4 agonist PP depressed the activity of GABA-expressing neurons mainly by presynaptic attenuation of glutamate release. Together, these results show that the family of neuropeptide Y modulators reduces the activity of inhibitory GABA neurons in the ARC by multiple presynaptic and postsynaptic mechanisms.
引用
收藏
页码:7406 / 7419
页数:14
相关论文
共 81 条
[1]   Glucagon-like peptide 1 excites hypocretin/orexin neurons by direct and indirect mechanisms: Implications for viscera-mediated arousal [J].
Acuna-Goycolea, C ;
van den Pol, A .
JOURNAL OF NEUROSCIENCE, 2004, 24 (37) :8141-8152
[2]   Group III metabotropic glutamate receptors maintain tonic inhibition of excitatory synaptic input to hypocretin/orexin neurons [J].
Acuna-Goycolea, C ;
Li, Y ;
van den Pol, AN .
JOURNAL OF NEUROSCIENCE, 2004, 24 (12) :3013-3022
[3]   MULTIPLE NEUROTRANSMITTERS IN THE TUBEROMAMMILLARY NUCLEUS - COMPARISON OF RAT, MOUSE, AND GUINEA-PIG [J].
AIRAKSINEN, MS ;
ALANEN, S ;
SZABAT, E ;
VISSER, TJ ;
PANULA, P .
JOURNAL OF COMPARATIVE NEUROLOGY, 1992, 323 (01) :103-116
[4]   Differential modulation of synaptic transmission by neuropeptide Y in rat neocortical neurons [J].
Bacci, A ;
Huguenard, JR ;
Prince, DA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (26) :17125-17130
[5]   AN ARCUATO-PARAVENTRICULAR AND ARCUATO-DORSOMEDIAL HYPOTHALAMIC NEUROPEPTIDE Y-CONTAINING SYSTEM WHICH LACKS NORADRENALINE IN THE RAT [J].
BAI, FL ;
YAMANO, M ;
SHIOTANI, Y ;
EMSON, PC ;
SMITH, AD ;
POWELL, JF ;
TOHYAMA, M .
BRAIN RESEARCH, 1985, 331 (01) :172-175
[6]   CLONING AND FUNCTIONAL EXPRESSION OF A HUMAN Y4 SUBTYPE RECEPTOR FOR PANCREATIC-POLYPEPTIDE, NEUROPEPTIDE-Y, AND PEPTIDE YY [J].
BARD, JA ;
WALKER, MW ;
BRANCHEK, TA ;
WEINSHANK, RL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) :26762-26765
[7]   Gut hormone PYY3-36 physiologically inhibits food intake [J].
Batterham, RL ;
Cowley, MA ;
Small, CJ ;
Herzog, H ;
Cohen, MA ;
Dakin, CL ;
Wren, AM ;
Brynes, AE ;
Low, MJ ;
Ghatei, MA ;
Cone, RD ;
Bloom, SR .
NATURE, 2002, 418 (6898) :650-654
[8]   QUANTAL ANALYSIS OF EPSCS RECORDED FROM SMALL NUMBERS OF SYNAPSES IN HIPPOCAMPAL CULTURES [J].
BEKKERS, JM ;
STEVENS, CF .
JOURNAL OF NEUROPHYSIOLOGY, 1995, 73 (03) :1145-1156
[9]   Local synaptic release of glutamate from neurons in the rat hypothalamic arcuate nucleus [J].
Belousov, AB ;
vandenPol, AN .
JOURNAL OF PHYSIOLOGY-LONDON, 1997, 499 (03) :747-761
[10]   ANORECTIC EFFECTS OF ESTROGEN MAY BE MEDIATED BY DECREASED NEUROPEPTIDE-Y RELEASE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS [J].
BONAVERA, JJ ;
DUBE, MG ;
KALRA, PS ;
KALRA, SP .
ENDOCRINOLOGY, 1994, 134 (06) :2367-2370