Feedforward inhibition controls the spread of granule cell-induced Purkinje cell activity in the cerebellar cortex.
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.
Santamaria
Fidel
F
Research Imaging Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-6240, USA.
Tripp
Patrick G
PG
Bower
James M
JM
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D005260:Female; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D016571:Neural Networks, Computer; D009434:Neural Pathways / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*