SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity
SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity
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DOI：
10.1523/jneurosci.0765-13.2013
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发表时间：
2013-06-19
影响因子：
5.3
通讯作者：
Rumbaugh, Gavin
中科院分区：
文献类型：
--
作者：
Clement, James P.;Ozkan, Emin D.;Rumbaugh, Gavin
发育可塑性的关键时期有助于神经连接的完善，从而广泛地塑造大脑发育。这些可塑性窗口被认为对感知、语言和认知的成熟非常重要。临界期下皮质区域的突触属性影响窗口的开始和持续时间，尽管目前尚不清楚塑造突触发育的机制如何改变临界期的属性。在这项研究中，我们证明了Syngap1的单个拷贝的失活，它导致了人类自闭症患者中一种令人惊讶的常见形式的散发性、非综合征性智力残疾，诱导了小鼠新皮质中兴奋性连接的广泛早期功能成熟。这种加速的功能成熟是在不同的新皮质区域和层次上观察到的，并直接影响了与经验相关的皮质地图精细化相关的突触可塑性关键期的持续时间。这些研究支持这样一种观点，即对突触成熟的遗传控制会影响关键期可塑性窗口的持续时间。这些数据还表明，关键时期的持续时间将突触成熟率与智力的发展联系起来。
Critical periods of developmental plasticity contribute to the refinement of neural connections that broadly shape brain development. These windows of plasticity are thought to be important for the maturation of perception, language, and cognition. Synaptic properties in cortical regions that underlie critical periods influence the onset and duration of windows, although it remains unclear how mechanisms that shape synapse development alter critical-period properties. In this study, we demonstrate that inactivation of a single copy of syngap1, which causes a surprisingly common form of sporadic, non-syndromic intellectual disability with autism in humans, induced widespread early functional maturation of excitatory connections in the mouse neocortex. This accelerated functional maturation was observed across distinct areas and layers of neocortex and directly influenced the duration of a critical-period synaptic plasticity associated with experience-dependent refinement of cortical maps. These studies support the idea that genetic control over synapse maturation influences the duration of critical-period plasticity windows. These data also suggest that critical-period duration links synapse maturation rates to the development of intellectual ability.