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J Neurophysiol (October 18, 2006). doi:10.1152/jn.01098.2005
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Submitted on October 18, 2005
Accepted on October 13, 2006

Feed-forward inhibition controls the spread of granule cell induced Purkinje cell activity in the cerebellar cortex

Fidel Santamaria1*, Patrick G Tripp2, and James Bower3

1 Computation and Neural Systems, California Institute of Technology, Pasadena, California, United States
2 Cajal Neuroscience Research Center, University of Texas, San Antonio, San Antonio, Texas, United States
3 Research Imaging Center, University of Texas Health Science Center, San Antonio, Texas, United States; Cajal Neuroscience Research Center, University of Texas, San Antonio, San Antonio, Texas, United States

* To whom correspondence should be addressed. E-mail: santamaria{at}neuro.duke.edu.

Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). While most theories of cerebellar function assume these synapses produce an excitatory sequential "beam-like" 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 due to the concomitant pf activation of feed-forward 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 only seen 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 feed-forward 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.







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