Prestori Francesca, Mapelli Lisa, D'Angelo Egidio
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
IRCCS Mondino Foundation, Pavia, Italy.
Front Mol Neurosci. 2019 Nov 7;12:267. doi: 10.3389/fnmol.2019.00267. eCollection 2019.
Neuronal inhibition can be defined as a spatiotemporal restriction or suppression of local microcircuit activity. The importance of inhibition relies in its fundamental role in shaping signal processing in single neurons and neuronal circuits. In this context, the activity of inhibitory interneurons proved the key to endow networks with complex computational and dynamic properties. In the last 50 years, the prevailing view on the functional role of cerebellar cortical inhibitory circuits was that excitatory and inhibitory inputs sum spatially and temporally in order to determine the motor output through Purkinje cells (PCs). Consequently, cerebellar inhibition has traditionally been conceived in terms of restricting or blocking excitation. This assumption has been challenged, in particular in the cerebellar cortex where all neurons except granule cells (and unipolar brush cells in specific lobules) are inhibitory and fire spontaneously at high rates. Recently, a combination of electrophysiological recordings and , imaging, optogenetics and computational modeling, has revealed that inhibitory interneurons play a much more complex role in regulating cerebellar microcircuit functions: inhibition neuronal response dynamics in the whole circuit and eventually regulate the PC output. This review elaborates current knowledge on cerebellar inhibitory interneurons [Golgi cells, Lugaro cells (LCs), basket cells (BCs) and stellate cells (SCs)], starting from their ontogenesis and moving up to their morphological, physiological and plastic properties, and integrates this knowledge with that on the more renown granule cells and PCs. We will focus on the circuit loops in which these interneurons are involved and on the way they generate feed-forward, feedback and lateral inhibition along with complex spatio-temporal response dynamics. In this perspective, inhibitory interneurons emerge as the real controllers of cerebellar functioning.
神经元抑制可定义为对局部微电路活动的时空限制或抑制。抑制的重要性在于其在塑造单个神经元和神经元回路信号处理过程中的基本作用。在这种情况下,抑制性中间神经元的活动被证明是赋予网络复杂计算和动态特性的关键。在过去的50年里,关于小脑皮质抑制性回路功能作用的主流观点是,兴奋性和抑制性输入在空间和时间上进行总和,以便通过浦肯野细胞(PCs)确定运动输出。因此,传统上认为小脑抑制是通过限制或阻断兴奋来实现的。这一假设受到了挑战,特别是在小脑皮质中,除颗粒细胞(以及特定小叶中的单极刷细胞)外,所有神经元都是抑制性的,并且以高频率自发放电。最近,电生理记录、成像、光遗传学和计算建模相结合,揭示了抑制性中间神经元在调节小脑微电路功能中发挥着更为复杂的作用:抑制整个回路中的神经元反应动力学,并最终调节PC输出。本综述阐述了关于小脑抑制性中间神经元[高尔基细胞、卢加罗细胞(LCs)、篮状细胞(BCs)和星状细胞(SCs)]的现有知识,从它们的个体发生开始,一直到它们的形态、生理和可塑性特性,并将这些知识与更著名的颗粒细胞和PCs的知识相结合。我们将关注这些中间神经元所参与的回路环,以及它们产生前馈、反馈和侧向抑制以及复杂时空反应动力学的方式。从这个角度来看,抑制性中间神经元成为小脑功能的真正控制器。