Aix-Marseille Université, INSERM, INMED, Marseille 13009, France.
Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
Proc Natl Acad Sci U S A. 2021 Nov 9;118(45). doi: 10.1073/pnas.2024890118.
Cerebellar Purkinje neurons integrate information transmitted at excitatory synapses formed by granule cells. Although these synapses are considered essential sites for learning, most of them appear not to transmit any detectable electrical information and have been defined as silent. It has been proposed that silent synapses are required to maximize information storage capacity and ensure its reliability, and hence to optimize cerebellar operation. Such optimization is expected to occur once the cerebellar circuitry is in place, during its maturation and the natural and steady improvement of animal agility. We therefore investigated whether the proportion of silent synapses varies over this period, from the third to the sixth postnatal week in mice. Selective expression of a calcium indicator in granule cells enabled quantitative mapping of presynaptic activity, while postsynaptic responses were recorded by patch clamp in acute slices. Through this approach and the assessment of two anatomical features (the distance that separates adjacent planar Purkinje dendritic trees and the synapse density), we determined the average excitatory postsynaptic potential per synapse. Its value was four to eight times smaller than responses from paired recorded detectable connections, consistent with over 70% of synapses being silent. These figures remained remarkably stable across maturation stages. According to the proposed role for silent synapses, our results suggest that information storage capacity and reliability are optimized early during cerebellar maturation. Alternatively, silent synapses may have roles other than adjusting the information storage capacity and reliability.
小脑浦肯野神经元整合由颗粒细胞形成的兴奋性突触传递的信息。尽管这些突触被认为是学习的重要部位,但其中大多数似乎没有传递任何可检测的电信息,因此被定义为沉默突触。有人提出,沉默突触是最大化信息存储容量并确保其可靠性所必需的,从而优化小脑的运作。这种优化预计会在小脑回路就位后发生,即在其成熟过程中和动物敏捷性的自然和稳定提高过程中。因此,我们研究了沉默突触的比例是否在此期间发生变化,从小鼠出生后的第三周到第六周。颗粒细胞中钙指示剂的选择性表达使我们能够对突触前活动进行定量映射,而在急性切片中通过膜片钳记录突触后反应。通过这种方法和对两个解剖学特征(分隔相邻平面浦肯野树突的距离和突触密度)的评估,我们确定了每个突触的平均兴奋性突触后电位。其值是来自配对记录的可检测连接的反应的四到八倍,这与超过 70%的突触处于沉默状态一致。这些数字在成熟阶段仍然非常稳定。根据沉默突触的预期作用,我们的结果表明,信息存储容量和可靠性在小脑成熟的早期就得到了优化。或者,沉默突触可能具有除了调整信息存储容量和可靠性之外的其他作用。