Santamaria Fidel, Tripp Patrick G, Bower James M
Research Imaging Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-6240, USA.
J Neurophysiol. 2007 Jan;97(1):248-63. doi: 10.1152/jn.01098.2005. Epub 2006 Oct 18.
Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). Although most theories of cerebellar function assume these synapses produce an excitatory sequential "beamlike" activation of PCs, numerous physiological studies have failed to find such beams. Using a computer model of the cerebellar cortex we predicted that the lack of PCs beams is explained by the concomitant pf activation of feedforward molecular layer inhibition. This prediction was tested, in vivo, by recording PCs sharing a common set of pfs before and after pharmacologically blocking inhibitory inputs. As predicted by the model, pf-induced beams of excitatory PC responses were seen only when inhibition was blocked. Blocking inhibition did not have a significant effect in the excitability of the cerebellar cortex. We conclude that pfs work in concert with feedforward cortical inhibition to regulate the excitability of the PC dendrite without directly influencing PC spiking output. This conclusion requires a significant reassessment of classical interpretations of the functional organization of the cerebellar cortex.
与小脑颗粒细胞的平行纤维（pf）轴突相关的突触构成了浦肯野细胞（PC）上最大的兴奋性输入。尽管大多数关于小脑功能的理论都假定这些突触会对浦肯野细胞产生兴奋性的顺序性“束状”激活，但众多生理学研究都未能找到这样的束状激活。利用小脑皮质的计算机模型，我们预测浦肯野细胞束状激活的缺失可以通过前馈分子层抑制的伴随pf激活来解释。通过在体内记录共享一组共同pf的浦肯野细胞在药理学阻断抑制性输入前后的情况，对这一预测进行了测试。正如模型所预测的，只有在抑制被阻断时，才会出现pf诱导的兴奋性浦肯野细胞反应束。阻断抑制对小脑皮质的兴奋性没有显著影响。我们得出结论，pf与前馈皮质抑制协同作用，以调节浦肯野细胞树突的兴奋性，而不直接影响浦肯野细胞的动作电位输出。这一结论需要对小脑皮质功能组织的经典解释进行重大重新评估。
