Siddoway Benjamin, Hou Hailong, Xia Houhui
Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Neuropharmacology. 2014 Mar;78:38-44. doi: 10.1016/j.neuropharm.2013.07.009. Epub 2013 Aug 2.
Homeostatic synaptic downscaling is a negative feedback response to chronic elevated network activity to reduce the firing rate of neurons. This form of synaptic plasticity decreases the strength of individual synapses to the same proportion, or in a multiplicative manner. Because of this, synaptic downscaling has been hypothesized to counter the potential run-away excitation due to Hebbian type of long term potentiation (LTP), while preserving relative synaptic weight encoded in individual synapses and thus memory information. In this article, we will review the current knowledge on the signaling and molecular mechanisms of synaptic downscaling. Specifically, we focus on three general areas. First the functional roles of several immediate early genes such as Plk2, Homer1a, Arc and Narp are discussed. Secondly, we examine the current knowledge on the regulation of synaptic protein levels by ubiquitination and transcriptional repression in synaptic downscaling. Thirdly, we review the dynamics of signaling molecules such as kinases and phosphatases critical for synaptic downscaling, and their regulation of synaptic scaffolding proteins. Finally we briefly discuss the heterogeneity of homeostatic synaptic downscaling mechanisms. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.
稳态突触缩微是对慢性升高的网络活动的一种负反馈反应，以降低神经元的放电频率。这种形式的突触可塑性以相同比例或以乘法方式降低单个突触的强度。因此，有人提出突触缩微可对抗由于赫布型长时程增强（LTP）导致的潜在失控兴奋，同时保留单个突触中编码的相对突触权重，从而保留记忆信息。在本文中，我们将综述关于突触缩微的信号传导和分子机制的当前知识。具体而言，我们关注三个主要领域。首先讨论几个即时早期基因如Plk2、Homer1a、Arc和Narp的功能作用。其次，我们研究关于在突触缩微中泛素化和转录抑制对突触蛋白水平调节的当前知识。第三，我们综述对突触缩微至关重要的信号分子如激酶和磷酸酶的动力学，以及它们对突触支架蛋白的调节。最后，我们简要讨论稳态突触缩微机制的异质性。本文是名为“稳态突触可塑性”的特刊的一部分。
