Centre for Research in Neuroscience, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montréal, Québec H3G 1A4, Canada.
Departments of Neurology and Neurosurgery, McGill University, Montréal, Québec H3G 1A4, Canada.
J Neurosci. 2024 Sep 11;44(37):e0455242024. doi: 10.1523/JNEUROSCI.0455-24.2024.
The cerebellum plays an important role in diverse brain functions, ranging from motor learning to cognition. Recent studies have suggested that molecular and cellular heterogeneity within cerebellar lobules contributes to functional differences across the cerebellum. However, the specific relationship between molecular and cellular heterogeneity and diverse functional outputs of different regions of the cerebellum remains unclear. Here, we describe a previously unappreciated form of synaptic heterogeneity at parallel fiber synapses to Purkinje cells in the mouse cerebellum (both sexes). In contrast to uniform fast synaptic transmission, we found that the properties of slow synaptic transmission varied by up to threefold across different lobules of the mouse cerebellum, resulting in surprising heterogeneity. Depending on the location of a Purkinje cell, the time of peak of slow synaptic currents varied by hundreds of milliseconds. The duration and decay time of these currents also spanned hundreds of milliseconds, based on lobule. We found that, as a consequence of the heterogeneous synaptic dynamics, the same brief input stimulus was transformed into prolonged firing patterns over a range of timescales that depended on Purkinje cell location.
小脑在多种大脑功能中发挥着重要作用,从运动学习到认知。最近的研究表明,小脑小叶内的分子和细胞异质性有助于小脑内不同区域的功能差异。然而,小脑不同区域的分子和细胞异质性与多样化功能输出之间的具体关系尚不清楚。在这里,我们描述了在雄性和雌性小鼠小脑浦肯野细胞的平行纤维突触中存在一种以前未被认识到的突触异质性形式。与均匀的快速突触传递相反,我们发现慢突触传递的性质在小鼠小脑的不同小叶之间变化可达三倍,导致惊人的异质性。取决于浦肯野细胞的位置,慢突触电流的峰值时间相差数百毫秒。这些电流的持续时间和衰减时间也基于小叶而跨越数百毫秒。我们发现,由于突触动力学的异质性,相同的短暂输入刺激在依赖于浦肯野细胞位置的一系列时间尺度上被转化为长时间的放电模式。