Grant Seth G N, Fransén Erik
Genes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Front Synaptic Neurosci. 2020 Oct 2;12:590403. doi: 10.3389/fnsyn.2020.590403. eCollection 2020.
Recent studies have shown an unexpectedly high degree of synapse diversity arising from molecular and morphological differences among individual synapses. Diverse synapse types are spatially distributed within individual dendrites, between different neurons, and across and between brain regions, producing the synaptome architecture of the brain. The spatial organization of synapse heterogeneity is important because the physiological activation of heterogeneous excitatory synapses produces a non-uniform spatial output of synaptic potentials, which confounds the interpretation of measurements obtained from population-averaging electrodes, optrodes and biochemical methods that lack single-synapse resolution. Population-averaging measurements cannot distinguish between changes in the composition of populations of synapses and changing synaptic physiology. Here we consider the implications of synapse diversity and its organization into synaptome architecture for studies of synapse physiology, plasticity, development and behavior, and for the interpretation of phenotypes arising from pharmacological and genetic perturbations. We conclude that prevailing models based on population-averaging measurements need reconsideration and that single-synapse resolution physiological recording methods are required to confirm or refute the major synaptic models of behavior.
最近的研究表明，由于单个突触之间的分子和形态差异，突触多样性程度出人意料地高。不同类型的突触在单个树突内、不同神经元之间以及大脑区域之间和内部进行空间分布，从而形成大脑的突触组结构。突触异质性的空间组织很重要，因为异质性兴奋性突触的生理激活会产生非均匀的突触电位空间输出，这会混淆从缺乏单突触分辨率的群体平均电极、光电极和生化方法获得的测量结果的解释。群体平均测量无法区分突触群体组成的变化和不断变化的突触生理学。在这里，我们考虑突触多样性及其在突触组结构中的组织对突触生理学、可塑性、发育和行为研究以及对药理学和基因扰动产生的表型解释的影响。我们得出结论，基于群体平均测量的主流模型需要重新考虑，并且需要单突触分辨率的生理记录方法来证实或反驳主要的行为突触模型。
