Department of Neurology and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.
J Neurosci. 2011 Nov 2;31(44):15932-43. doi: 10.1523/JNEUROSCI.0742-11.2011.
Approximately one-fourth of the neurons in Caenorhabditis elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA(A) receptor agonists, indicating that postsynaptic mechanisms contribute to lethargus-dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species.
秀丽隐杆线虫成虫约四分之一的神经元在幼虫发育过程中产生，这表明幼虫神经系统结构具有巨大的可塑性。幼虫发育过程中在昏眠期表现出类似睡眠的静止行为周期性表达，而昏眠期发生在幼虫发育阶段过渡时期。我们使用乙酰胆碱酯酶抑制剂 aldicarb 研究了昏眠期间神经肌肉接头的可塑性。动物在暴露于 aldicarb 时的收缩率受肌肉上兴奋性胆碱能和抑制性 GABA 能输入之间的平衡控制。在昏眠期间，收缩率会加速。突变分析和光遗传学研究表明，在昏眠期间 GABA 能突触传递减少。处于昏眠状态的线虫对 GABA(A)受体激动剂表现出部分抗性，表明突触后机制有助于与昏眠相关的可塑性。使用将静止状态与发育阶段分离的遗传操作，我们表明突触可塑性依赖于发育时间，而不依赖于动物的行为状态。我们提出，秀丽隐杆线虫发育时钟调节的突触可塑性类似于其他物种生物钟调节的突触可塑性。
