A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.
Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions.
UMR 8118, CNRS and Université Paris Descartes, 75006 Paris, France, Center for Theoretical Neuroscience, Columbia University, New York, New York, 10032, Department of Bioengineering, Imperial College London, SW7 2AZ London, United Kingdom.
Claudia
C
Clopath
Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts and Sciences, 1000 GC Amsterdam, The Netherlands, Department of Neuroscience, Erasmus MC, 3015 GD Rotterdam, The Netherlands, Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, and.
Aleksandra
A
Badura
Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts and Sciences, 1000 GC Amsterdam, The Netherlands, Department of Neuroscience, Erasmus MC, 3015 GD Rotterdam, The Netherlands, c.dezeeuw@erasmusmc.nl nbrunel@galton.uchicago.edu.
Chris I
CI
De Zeeuw
UMR 8118, CNRS and Université Paris Descartes, 75006 Paris, France, Departments of Statistics and Neurobiology, University of Chicago, Chicago, Illinois 60637 c.dezeeuw@erasmusmc.nl nbrunel@galton.uchicago.edu.
Nicolas
N
Brunel
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003198:Computer Simulation; D005133:Eye Movements / Q000235:genetics; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000502:physiology*; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D017711:Nonlinear Dynamics; D011689:Purkinje Cells / Q000502:physiology; D018079:Receptors, GABA / Q000235:genetics; D011963:Receptors, GABA-A; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics*; D027981:Symporters / Q000235:genetics; D013569:Synapses / Q000235:genetics; D000096922:K Cl- Cotransporters
D018079:Receptors, GABA; D011963:Receptors, GABA-A; D027981:Symporters; D000096922:K Cl- Cotransporters; C470436:Gabrb2 protein, mouse