title: Effects of climbing fiber driven inhibition on Purkinje neuron spiking.
abstract: Climbing fiber (CF) input to the cerebellum is thought to instruct associative motor memory formation through its effects on multiple sites within the cerebellar circuit. We used adeno-associated viral delivery of channelrhodopsin-2 (ChR2) to inferior olivary neurons to selectively express ChR2 in CFs, achieving nearly complete transfection of CFs in the caudal cerebellar lobules of rats. As expected, optical stimulation of ChR2-expressing CFs generates complex spike responses in individual Purkinje neurons (PNs); in addition we found that such stimulation recruits a network of inhibitory interneurons in the molecular layer. This CF-driven disynaptic inhibition prolongs the postcomplex spike pause observed when spontaneously firing PNs receive direct CF input; such inhibition also elicits pauses in spontaneously firing PNs not receiving direct CF input. Baseline firing rates of PNs are strongly suppressed by low-frequency (2 Hz) stimulation of CFs, and this suppression is partly relieved by blocking synaptic inhibition. We conclude that CF-driven, disynaptic inhibition has a major influence on PN excitability and contributes to the widely observed negative correlation between complex and simple spike rates. Because they receive input from many CFs, molecular layer interneurons are well positioned to detect the spatiotemporal patterns of CF activity believed to encode error signals. Together, our findings suggest that such inhibition may bind together groups of Purkinje neurons to provide instructive signals to downstream sites in the cerebellar circuit.
authors.affiliation: Department of Neurobiology, Brain Research Institute, and Integrative Center for Learning and Memory, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mathews
authors.forename: Ka Hung
authors.initials: KH
authors.lastname: Lee
authors.forename: Zechun
authors.initials: Z
authors.lastname: Peng
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Houser
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Otis
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009847:Olivary Nucleus / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley