Neurology and Research Services, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH, 44106, USA.
Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
Cerebellum. 2022 Dec;21(6):879-904. doi: 10.1007/s12311-021-01332-w. Epub 2021 Oct 19.
Purkinje cells (PCs) in the cerebellar flocculus carry rate-coded information that ultimately drives eye movement. Floccular PCs lying nearby each other exhibit partial synchrony of their simple spikes (SS). Elsewhere in the cerebellum, PC SS synchrony has been demonstrated to influence activity of the PCs' synaptic targets, and some suggest it constitutes another vector for information transfer. We investigated in the cerebellar flocculus the extent to which the rate code and PC synchrony interact. One motivation for the study was to explain the cerebellar deficits in ataxic mice like tottering; we speculated that PC synchrony has a positive effect on rate code transmission that is lost in the mutants. Working in transgenic mice whose PCs express channelrhodopsin, we exploited a property of optogenetics to control PC synchrony: pulsed photostimulation engenders stimulus-locked spiking, whereas continuous photostimulation engenders spiking whose timing is unconstrained. We photoactivated flocculus PCs using pulsed stimuli with sinusoidally varying timing vs. continuous stimuli with sinusoidally varying intensity. Recordings of PC pairs confirmed that pulsed stimuli engendered greater PC synchrony. We quantified the efficiency of transmission of the evoked PC firing rate modulation from the amplitudes of firing rate modulation and eye movement. Rate code transmission was slightly poorer in the conditions that generated greater PC synchrony, arguing against our motivating speculation regarding the origin of ataxia in tottering. Floccular optogenetic stimulation prominently augmented a 250-300 Hz local field potential oscillation, and we demonstrate relationships between the oscillation power and the evoked PC synchrony.
浦肯野细胞（PCs）在小脑绒球传递速率编码信息，这些信息最终驱动眼球运动。彼此相邻的绒球 PCs 表现出简单峰电位（SS）的部分同步。在小脑的其他部位，已经证明 PC SS 同步会影响 PC 突触靶点的活动，并且有人认为它构成了另一种信息传递载体。我们在小脑绒球中研究了速率编码和 PC 同步之间的相互作用程度。进行这项研究的一个动机是解释像 tottering 这样的共济失调小鼠的小脑缺陷；我们推测 PC 同步对速率编码传输有积极影响，而在突变体中这种影响丢失了。在表达通道视紫红质的转基因小鼠中工作，我们利用光遗传学的一个特性来控制 PC 同步：脉冲光刺激会产生与刺激锁相的尖峰，而连续光刺激会产生不受时间限制的尖峰。我们使用脉冲刺激（其定时呈正弦变化）和连续刺激（其强度呈正弦变化）来对绒球 PCs 进行光激活。对 PC 对的记录证实，脉冲刺激会产生更大的 PC 同步。我们通过尖峰率调制的幅度和眼球运动来量化从刺激诱发的 PC 发放率调制的传输效率。在产生更大 PC 同步的条件下，诱发的 PC 发放率调制的传输效率略有降低，这与 tottering 中共济失调起源的动机推测相矛盾。绒球的光遗传刺激显著增强了 250-300 Hz 的局部场电位振荡，我们证明了振荡功率与诱发的 PC 同步之间的关系。
