Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.
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DOI:
10.1038/s41593-020-0701-z
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发表时间:
2020-11
影响因子:
25
通讯作者:
Regehr WG
Regehr WG
中科院分区:
医学1区
文献类型:
--
作者:
Han KS;Chen CH;Khan MM;Guo C;Regehr WG

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来自下橄榄体 (IO) 的攀爬纤维 (CF) 在小脑浦肯野细胞 (PC) 树突上产生强烈的兴奋性突触,并触发称为复杂尖峰 (CS) 的独特反应。我们发现,在清醒的小鼠中,一台 PC 中的 CS 会抑制相邻 PC 中的传统简单尖峰 (SS) 几毫秒。这涉及一种新颖的突触耦合,其中兴奋性突触产生大量负性细胞外信号,非突触性地抑制邻近的 PC。 CS-SS 触觉信号的距离依赖性与已知的 CF 散度相结合,允许单个 IO 神经元通过同步抑制可能超过一百个 PC 的放电来影响小脑的输出。体内光遗传学研究和切片动态钳研究表明,这种短暂的 PC 抑制,无论是由于触觉信号传导还是其他机制,都可以以惊人的速度和精度有效促进小脑深部核团神经元的放电。
Climbing fibers (CFs) from the inferior olive (IO) make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites, and trigger distinctive responses known as complex spikes (CSs). We find that in awake mice, a CS in one PC suppresses conventional simple spikes (SSs) in neighboring PCs for several milliseconds. This involves a novel ephaptic coupling, in which an excitatory synapse generates large negative extracellular signals that nonsynaptically inhibit neighboring PCs. The distance dependence of CS-SS ephaptic signaling, combined with the known CF divergence, allows a single IO neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over one hundred PCs. Optogenetic studies in vivo, and dynamic clamp studies in slice, indicate that such brief PC suppression, either as a result of ephaptic signaling or other mechanisms, can effectively promote firing in neurons in the deep cerebellar nuclei with remarkable speed and precision.
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