Jo Young-Hwan, Role Lorna W
Department of Anatomy and Cell Biology in the Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
J Neurophysiol. 2002 Nov;88(5):2501-8. doi: 10.1152/jn.00352.2002.
The lateral hypothalamus (LH) is an important center for the integration of autonomic and limbic information and is implicated in the modulation of visceral motor and sensory pathways, including those underlying feeding and arousal behaviors. LH neurons in vitro release both ATP and GABA. The control of ATP and GABA co-transmission in LH may underlie the participation of LH in basic aspects of arousal and reinforcement. LH neurons receive cholinergic input from the pedunculopontine and laterodorsal tegmental nuclei as well as from cholinergic interneurons within the LH per se. This study presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated enhancement of GABAergic, but not of purinergic, transmission despite the co-transmission of ATP and GABA at LH synapses in vitro. Facilitation of GABAergic transmission by nicotine is inhibited by antagonists of (alphabeta)*-containing nAChRs, but is unaffected by an alpha7-selective antagonist, consistent with a nAChR-mediated enhancement of GABA release mediated by non-alpha7-containing nAChRs. Activation of muscarinic ACh receptors enhances the release of ATP while concomitantly depressing GABAergic transmission. The independent modulation of ATP/GABAergic transmission may provide a new level of synaptic flexibility in which individual neurons utilize more than one neurotransmitter but retain independent control over their synaptic activity.
外侧下丘脑（LH）是自主神经和边缘系统信息整合的重要中枢，与内脏运动和感觉通路的调节有关，包括那些与进食和觉醒行为相关的通路。体外培养的LH神经元可释放ATP和GABA。LH中ATP和GABA共同传递的调控可能是LH参与觉醒和强化基本过程的基础。LH神经元接受来自脚桥核和外侧背盖核的胆碱能输入，以及来自LH本身胆碱能中间神经元的输入。本研究提供了证据，表明烟碱型乙酰胆碱受体（nAChR）介导增强GABA能传递，但不增强嘌呤能传递，尽管体外LH突触处存在ATP和GABA的共同传递。尼古丁对GABA能传递的促进作用被含（αβ）*的nAChR拮抗剂抑制，但不受α7选择性拮抗剂的影响，这与由不含α7的nAChR介导的GABA释放增强一致。毒蕈碱型ACh受体的激活增强ATP的释放，同时抑制GABA能传递。ATP/GABA能传递的独立调节可能提供了一种新的突触灵活性水平，其中单个神经元利用不止一种神经递质，但对其突触活动保持独立控制。
