Helekar S A, Noebels J L
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4736-40. doi: 10.1073/pnas.88.11.4736.
A mutation at the tottering locus (tg, recessive, on chromosome 8) stimulates noradrenergic locus coeruleus axon terminal outgrowth and predisposes the brain to generalized spike-wave epilepsy in the young mouse. In an isolated synaptic circuit studied in vitro, the hyperinnervated mutant hippocampal pyramidal neurons respond normally when individually activated; however, latent neuronal signaling defects emerge during synchronous network bursting, revealing two conditional excitability phenotypes: a voltage-dependent prolongation of a complex synaptic response, the paroxysmal depolarizing shift, and a beta-adrenoreceptor-linked attenuation of the afterhyperpolarization. In this target brain region, the tg locus transforms neuronal excitability without altering measured intrinsic membrane properties, indicating that gene control of inherited epileptic traits may be mediated in part by activity-dependent modulation of network behavior favoring synchronous neuronal firing.
蹒跚基因座（tg，隐性，位于8号染色体上）的突变会刺激去甲肾上腺素能蓝斑轴突终末生长，并使幼鼠大脑易患全身性棘波癫痫。在体外研究的一个孤立突触回路中，超神经支配的突变海马锥体细胞在单独激活时反应正常；然而，在同步网络爆发期间会出现潜在的神经元信号缺陷，揭示出两种条件性兴奋性表型：复合突触反应（阵发性去极化偏移）的电压依赖性延长，以及超极化后电位的β-肾上腺素能受体相关衰减。在这个目标脑区，tg基因座改变了神经元兴奋性，而未改变测得的内在膜特性，这表明遗传性癫痫特征的基因控制可能部分是通过对有利于同步神经元放电的网络行为进行活动依赖性调节来介导的。
