Luz Liliana L, Currie Stephen P, Daw Michael I
Centre for Integrative Physiology, George Square, University of Edinburgh, Edinburgh, United Kingdom.
PLoS One. 2017 Feb 8;12(2):e0171897. doi: 10.1371/journal.pone.0171897. eCollection 2017.
New synapses are constantly being generated and lost in the living brain with only a subset of these being stabilized to form an enduring component of neuronal circuitry. The properties of synaptic transmission have primarily been established in a variety of in vitro neuronal preparations. It is not clear, however, if newly-formed and persistent synapses contribute to the results of these studies consistently throughout the lifespan of these preparations. In neonatal somatosensory, barrel, cortex we have previously hypothesized that a population of thalamocortical synapses displaying unusually slow kinetics represent newly-formed, default-transient synapses. This clear phenotype would provide an ideal tool to investigate if such newly formed synapses consistently contribute to synaptic transmission throughout a normal experimental protocol. We show that the proportion of synapses recorded in vitro displaying slow kinetics decreases with time after brain slice preparation. However, slow synapses persist in vitro in the presence of either minocycline, an inhibitor of microglia-mediated synapse elimination, or the TrkB agonist 7,8-dihydroxyflavone a promoter of synapse formation. These findings show that the observed properties of synaptic transmission may systematically change with time in vitro in a standard brain slice preparation.
在活体大脑中,新的突触不断产生和消失,只有其中一部分会稳定下来,形成神经元回路的持久组成部分。突触传递的特性主要是在各种体外神经元制备物中确定的。然而,尚不清楚新形成的和持久的突触在这些制备物的整个寿命期间是否始终对这些研究结果有贡献。在新生小鼠体感皮层的桶状皮质中,我们之前曾假设,一群显示出异常缓慢动力学的丘脑皮质突触代表新形成的、默认短暂的突触。这种明确的表型将提供一个理想的工具,用于研究这些新形成的突触在整个正常实验方案中是否始终对突触传递有贡献。我们发现,在脑片制备后,体外记录到的显示缓慢动力学的突触比例会随着时间下降。然而,在存在小胶质细胞介导的突触消除抑制剂米诺环素或TrkB激动剂7,8-二羟基黄酮(一种突触形成促进剂)的情况下,缓慢突触会在体外持续存在。这些发现表明,在标准脑片制备中,观察到的突触传递特性可能会随着体外时间而系统性地改变。