Suter K J, Wuarin J P, Smith B N, Dudek F E, Moenter S M
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
Endocrinology. 2000 Oct;141(10):3731-6. doi: 10.1210/endo.141.10.7690.
Central control of reproduction is governed by a neuronal pulse generator that underlies the activity of hypothalamic neuroendocrine cells that secrete GnRH. Bursts and prolonged episodes of repetitive action potentials have been associated with hormone secretion in this and other neuroendocrine systems. To begin to investigate the cellular mechanisms responsible for the GnRH pulse generator, we used transgenic mice in which green fluorescent protein was genetically targeted to GnRH neurons. Whole-cell recordings were obtained from 21 GnRH neurons, visually identified in 200-microm preoptic/hypothalamic slices, to determine whether they exhibit high frequency bursts of action potentials and are electrically coupled at or near the somata. All GnRH neurons fired spontaneous action potentials, and in 15 of 21 GnRH neurons, the action potentials occurred in single bursts or episodes of repetitive bursts of high frequency spikes (9.77 +/- 0.87 Hz) lasting 3-120 sec. Extended periods of quiescence of up to 30 min preceded and followed these periods of repetitive firing. Examination of 92 GnRH neurons (including 32 neurons that were located near another green fluorescent protein-positive neuron) revealed evidence for coupling in only 1 pair of GnRH neurons. The evidence for minimal coupling between these neuroendocrine cells suggests that direct soma to soma transfer of information, through either cytoplasmic bridges or gap junctions, has a minor role in synchronization of GnRH neurons. The pattern of electrical activity observed in single GnRH neurons within slices is temporally consistent with observations of GnRH release and multiple unit electrophysiological correlates of LH release. Episodes of burst firing of individual GnRH neurons may represent a component of the GnRH pulse generator.
生殖的中枢控制由一个神经元脉冲发生器调控，该脉冲发生器是下丘脑神经内分泌细胞分泌促性腺激素释放激素（GnRH）活动的基础。在这个以及其他神经内分泌系统中，爆发性和持续性的重复动作电位与激素分泌有关。为了开始研究负责GnRH脉冲发生器的细胞机制，我们使用了转基因小鼠，其中绿色荧光蛋白通过基因靶向作用于GnRH神经元。从200微米视前区/下丘脑切片中视觉识别出的21个GnRH神经元获得全细胞记录，以确定它们是否表现出高频动作电位爆发，以及在胞体处或附近是否存在电耦合。所有GnRH神经元均自发产生动作电位，在21个GnRH神经元中的15个中，动作电位以单个爆发或高频尖峰重复爆发（9.77±0.87赫兹）的形式出现，持续3 - 120秒。在这些重复放电期之前和之后有长达30分钟的静息期。对92个GnRH神经元（包括32个位于另一个绿色荧光蛋白阳性神经元附近的神经元）的检查仅发现一对GnRH神经元存在耦合证据。这些神经内分泌细胞之间耦合极少的证据表明，通过胞质桥或缝隙连接进行的直接胞体到胞体的信息传递在GnRH神经元同步化中起次要作用。在切片内单个GnRH神经元中观察到的电活动模式在时间上与GnRH释放的观察结果以及促黄体生成素（LH）释放的多单位电生理相关性一致。单个GnRH神经元的爆发性放电期可能代表GnRH脉冲发生器的一个组成部分。
