Department of Neurobiology, Northwestern University, Evanston, IL, USA.
Department of Neurobiology, Northwestern University, Evanston, IL, USA; Northwestern University Interdepartmental Neuroscience Program, Northwestern University, Evanston, IL, USA.
Neuron. 2024 Jun 5;112(11):1848-1861.e4. doi: 10.1016/j.neuron.2024.02.014. Epub 2024 Mar 15.
Whisker stimulation in awake mice evokes transient suppression of simple spike probability in crus I/II Purkinje cells. Here, we investigated how simple spike suppression arises synaptically, what it encodes, and how it affects cerebellar output. In vitro, monosynaptic parallel fiber (PF)-excitatory postsynaptic currents (EPSCs) facilitated strongly, whereas disynaptic inhibitory postsynaptic currents (IPSCs) remained stable, maximizing relative inhibitory strength at the onset of PF activity. Short-term plasticity thus favors the inhibition of Purkinje spikes before PFs facilitate. In vivo, whisker stimulation evoked a 2-6 ms synchronous spike suppression, just 6-8 ms (∼4 synaptic delays) after sensory onset, whereas active whisker movements elicited broadly timed spike rate increases that did not modulate sensory-evoked suppression. Firing in the cerebellar nuclei (CbN) inversely correlated with disinhibition from sensory-evoked simple spike suppressions but was decoupled from slow, non-synchronous movement-associated elevations of Purkinje firing rates. Synchrony thus allows the CbN to high-pass filter Purkinje inputs, facilitating sensory-evoked cerebellar outputs that can drive movements.
在清醒的小鼠中,胡须刺激会引起 I/II 小脑浦肯野细胞简单锋电位概率的短暂抑制。在这里,我们研究了简单锋电位抑制是如何在突触上产生的,它编码了什么,以及它如何影响小脑输出。在体外,单突触平行纤维(PF)兴奋性突触后电流(EPSC)强烈促进,而双突触抑制性突触后电流(IPSC)保持稳定,在 PF 活动开始时最大程度地提高了相对抑制强度。因此,短期可塑性有利于在 PF 促进之前抑制浦肯野细胞的锋电位。在体内,胡须刺激会引起 2-6ms 的同步锋电位抑制,仅在感觉开始后 6-8ms(∼4 个突触延迟),而主动胡须运动则引起广泛定时的锋电位率增加,不会调节感觉诱发的抑制。小脑核(CbN)的放电与感觉诱发的简单锋电位抑制的去抑制呈反相关,但与浦肯野细胞放电率的缓慢、非同步运动相关的升高脱钩。因此,同步允许 CbN 对浦肯野细胞输入进行高通滤波,促进可以驱动运动的感觉诱发的小脑输出。