Department of Physiology, University of Pavia and National Consortium for the Physics of Matter, Via Forlanini 6, Pavia, Italy.
J Neurophysiol. 2010 Jan;103(1):250-61. doi: 10.1152/jn.00642.2009. Epub 2009 Nov 11.
The granular layer of cerebellum has been long hypothesized to perform combinatorial operations on incoming signals. Although this assumption is at the basis of main computational theories of cerebellum, it has never been assessed experimentally. Here, by applying high-resolution voltage-sensitive dye imaging techniques, we show that simultaneous activation of two partially overlapping mossy fiber bundles (either with single pulses or high-frequency bursts) can cause combined excitation and combined inhibition, which are compatible with the concepts of coincidence detection and spatial pattern separation predicted by theory. Combined excitation appeared as an area in which the combination of two inputs is greater than the arithmetic sum of the individual inputs and was enhanced by gamma-aminobutyric acid type A (GABA(A)) receptor blockers. Combined inhibition was manifest as an area where two inputs combined resulted in a reduction to less than half of the activity evoked from either one of the two inputs alone and was prevented by GABA(A) receptor blockers. The combinatorial responses occupied small granular layer regions (approximately 30 microm diameter), with combined inhibition being interspersed among extended areas of combined excitation. Moreover, the combinatorial effects lasted for tens of milliseconds and combined inhibition occurred only after termination of the stimuli. These combinatorial operations, if engaged by natural input patterns in vivo, may be important to influence incoming impulses organizing spatiotemporal spike sequences to be relayed to Purkinje cells.
小脑颗粒层长期以来被假设为对传入信号进行组合操作。尽管这一假设是小脑主要计算理论的基础，但它从未在实验中得到评估。在这里，我们通过应用高分辨率电压敏感染料成像技术，表明同时激活两个部分重叠的苔藓纤维束（无论是单个脉冲还是高频爆发）都可以引起组合兴奋和组合抑制，这与理论预测的巧合检测和空间模式分离的概念是一致的。组合兴奋表现为两个输入的组合大于单个输入的算术和的区域，并且被γ-氨基丁酸 A 型 (GABA(A)) 受体阻滞剂增强。组合抑制表现为两个输入组合导致的活动减少到单个输入的一半以下的区域，并且被 GABA(A) 受体阻滞剂阻止。组合反应占据小脑颗粒层的小区域（约 30 微米直径），组合抑制散布在组合兴奋的扩展区域之间。此外，组合效应持续数十毫秒，并且仅在刺激终止后才发生组合抑制。如果这些组合操作通过体内的自然输入模式参与，可能对影响传入冲动、组织时空尖峰序列以传递到浦肯野细胞很重要。
