Homeostatic synaptic scaling: molecular regulators of synaptic AMPA-type glutamate receptors.
Homeostatic synaptic scaling: molecular regulators of synaptic AMPA-type glutamate receptors.
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DOI：
10.12688/f1000research.13561.1
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hell JW
中科院分区：
文献类型：
--
作者：
Chowdhury D;Hell JW
神经元和电路在适当的动态范围内通过稳态机制保持其兴奋和活性水平，这对于大脑功能是基础的。它涉及一个负面反馈过程补偿总体输入的增加或减少，从而防止神经元超级或性能降低，否则可能会导致神经元网络功能障碍，而突触量表是良好的，我们对基本分子机制的理解仍在通过上调（升级）或下调（降尺度）的功能可用性实现了强度（AMPAR）在突触后部位。了解合成AMPAR如何根据整体神经元活动的改变而进行调节，这对于获得神经元网络如何适应其环境的变化以及一系列神经系统障碍的起源至关重要。在这里，我们讨论在调整突触后AMPAR的突触丰度以维持突触的突触丰度时所暗示的关键分子机制稳态。
The ability of neurons and circuits to maintain their excitability and activity levels within the appropriate dynamic range by homeostatic mechanisms is fundamental for brain function. Neuronal hyperactivity, for instance, could cause seizures. One such homeostatic process is synaptic scaling, also known as synaptic homeostasis. It involves a negative feedback process by which neurons adjust (scale) their postsynaptic strength over their whole synapse population to compensate for increased or decreased overall input thereby preventing neuronal hyper- or hypoactivity that could otherwise result in neuronal network dysfunction. While synaptic scaling is well-established and critical, our understanding of the underlying molecular mechanisms is still in its infancy. Homeostatic adaptation of synaptic strength is achieved through upregulation (upscaling) or downregulation (downscaling) of the functional availability of AMPA-type glutamate receptors (AMPARs) at postsynaptic sites. Understanding how synaptic AMPARs are modulated in response to alterations in overall neuronal activity is essential to gain valuable insights into how neuronal networks adapt to changes in their environment, as well as the genesis of an array of neurological disorders. Here we discuss the key molecular mechanisms that have been implicated in tuning the synaptic abundance of postsynaptic AMPARs in order to maintain synaptic homeostasis.