Li Ying, van den Pol Anthony N
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Neurosci. 2009 Dec 2;29(48):15195-204. doi: 10.1523/JNEUROSCI.4203-09.2009.
In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.
与皮质和海马体中γ-氨基丁酸（GABA）神经元的局部轴突不同，含有促黑素细胞激素（MCH）和GABA的下丘脑外侧神经元向整个大脑发送长轴突，并在能量稳态和精神状态中发挥关键作用。在成年期，MCH神经元维持超极化膜电位，并且大多数突触输入是抑制性的。相比之下，我们发现发育中的MCH神经元接受了更多的兴奋性突触输入。基于对MCH绿色荧光蛋白转基因小鼠下丘脑切片进行的短杆菌肽穿孔膜片钳记录，我们发现，在胚胎期和新生儿期直至出生后第10天，GABA是主要的兴奋性突触递质。令人惊讶的是，谷氨酸即使有兴奋性作用也很微小。GABA在发育中的MCH神经元中发挥复杂作用，其作用条件依赖于多种因素。GABA去极化可独立导致动作电位增加，或与其他去极化刺激叠加导致动作电位增加，或者根据其他去极化事件的相对时间，交替导致分流抑制。从去极化到超极化的发育转变在树突中比在细胞体中发生得更晚。早期GABA去极化基于Cl⁻依赖性内向电流。成熟神经元中在初始超极化之后出现的有趣的继发性去极化基于碳酸氢盐机制。因此，在食物消耗高的早期发育阶段，MCH神经元比成年期更去极化，并且这些促食欲细胞兴奋性突触输入水平的增加是由GABA介导的。
