Synaptic activity in X-linked mental retardation: a thorny issue.
Synaptic activity in X-linked mental retardation: a thorny issue.
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X连锁智力低下的突触活动：一个棘手的问题。
DOI：
10.1113/jphysiol.2011.226019
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Martina,Marco
中科院分区：
文献类型：
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作者：
Martina,Marco
与谷氨酸能神经元的兴奋性突触接触在很大程度上定位于树突棘，树突棘是一种特殊的突触后结构，允许个体输入的功能分离；因此，脊椎密度被用作突触数量的间接测量。然而，脊柱存在的根本原因尚不完全清楚，因为抑制性神经元甚至在棘刺树突中也能对突触输入产生严格的功能隔离（Goldberg et al. 2003）。已经提出了几个假设来解释脊髓定位的兴奋性突触传递的潜在优势，包括允许对树突周围的空间进行更有效的采样，并提供电和生化隔离，从而导致分布式网络中输入的线性整合（Yuste, 2011）。然而，独立于详细的作用，脊柱数量和突触传递之间的直接关联的想法似乎是无可争议的。与这一观点一致的是，主要的神经精神疾病通常伴随着脊柱数量的减少和/或脊柱形态的改变，尽管并不总是清楚异常的脊柱是否导致功能失调的电路，反之亦然。在这一期的《生理学杂志》上，Powell等人报道了一项关于寡肽-1缺失小鼠的研究结果，这是一种x连锁智力迟钝的啮齿动物模型，涉及突触前和突触后均表达的蛋白质。作者表明，在这些小鼠的海马切片中，突触传递的兴奋性和抑制性成分都被破坏了；此外，oligophrenin-1的缺乏也与脊柱密度降低有关。有趣的是，他们发现用Rho信号级联抑制剂对切片进行短时间（20分钟）的药物治疗
Excitatory synaptic contacts onto glutamatergic neurons are in large part localized on dendritic spines, which are specialized post-synaptic structures that allow functional segregation of individual inputs; consequently, spine density is used as an indirect measure of synapse number. Yet, the fundamental reason for spine existence is not completely clear, as inhibitory neurons can generate strict functional segregation of synaptic inputs even in aspiny dendrites (Goldberg et al. 2003). Several hypotheses have been put forward to explain the potential advantages of spine-located excitatory synaptic transmission, including allowing a more effective sampling of the space surrounding the dendrite and providing electrical and biochemical segregation that result in linear integration of inputs in distributed networks (Yuste, 2011). Independently of the detailed role, however, the idea of a direct correlation between spine number and synaptic transmission appears undisputable. In keeping with this idea, major neuropsychiatric disorders are normally accompanied by decreases in spine number and/or spine morphological alterations although it is not always clear whether abnormal spines lead to dysfunctional circuits or vice versa. In this issue of The Journal of Physiology, Powell et al. report the results of a study on oligophrenin-1-lacking mice, a rodent model of X-linked mental retardation that involves a protein that is expressed both pre-and postsynaptically. The authors show that in hippocampal slices from these mice both the excitatory and inhibitory components of synaptic transmission are disrupted; additionally, lack of oligophrenin-1 is also associated with decreased spine density. Intriguingly, they found that a short (20 min) pharmacological treatment of the slices with inhibitors of the Rho signalling cascade