Max Planck Institute for Dynamics and Self-Organization -- Department for Nonlinear Dynamics and Network Dynamics Group
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Tuesday, 11.12.2012 17 c.t.

Cerebellar learning - A model of vestibulo-ocular reflex adaptation

by Dr. Claudia Clopath
from Center for Theoretical Neuroscience, Columbia University, New York, USA

Contact person: Fred Wolf


Ludwig Prandtl lecture hall


The cerebellum is crucial for different types of motor learning. Established theories ofcerebellar learning posit that the cerebellum learns by adjusting the weights ofParallel Fiber (PF) to Purkinje cells (PC) synapses, thanks to teaching signals providedby Climbing Fiber inputs. While these theories are consistent with a large body ofexperimental data, in particular on synaptic plasticity in PF to PC synapses,they cannot easily explain a growing body of experimental work, that seems to indicatea significant role of other sites of plasticity. Recent advances in the developmentof a large number in transgenic animals, as well as behavioral and electrophysiogicalcomparative studies between these animals and wild-type animals, have openedan unprecedented window into the mechanisms underlying learning in this structure. Inparticular, it has been shown that specific knock-outs are impaired selectively on difficultvariants of the vestibulo-ocular reflex (VOR) adaptation task, one of the most studiedcerebellar-dependent motor learning tasks. These impairments occur even thoughthe classical plasticity mechanisms are left untouched. These data pose significant newchallenges for established models of cerebellar learning. The main goal of the present study is to better understand the mechanisms of learningin the cerebellum, through the construction of a model that can reproduce the availabledata on VOR adaptation, in both wild-type and transgenic animals. For this purpose, weperform in vivo electrophysiolgy recordings measuring simple spikes and complex spikes ofPurkinje Cells before and after learning. We then propose a model that includes some ofthe main cell types involved in this task: granule cells (GCs), the input layer of cerebellarcortex, that receives vestibular information from the mossy fibers (MFs); Purkinje cells(PCs), as well as molecular layer interneurons (INs); and two cell populations in themedial vestibular nuclei (MVN), one excitatory and one inhibitory, that together controleye movement. The model also includes two sites of learning: the classical GC to PFplasticity site, as well as plasticity in the MF to MVN synapses. We provide a mechanisticunderstanding on how the system learns VOR adaptation in normal conditions, as well ashow the system is impaired by specific knock-outs, which selectively suppress inhibitiononto PCs, or increase the excitability of GCs. Finally, we show that our modelis consistent with our in vivo electrophysiological recordings.

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