Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning.
Although feedforward inhibition onto Purkinje cells was first documented 40 years ago, we understand little of how inhibitory interneurons contribute to cerebellar function in behaving animals. Using a mouse line (PC-Deltagamma2) in which GABA(A) receptor-mediated synaptic inhibition is selectively removed from Purkinje cells, we examined how feedforward inhibition from molecular layer interneurons regulates adaptation of the vestibulo-ocular reflex. Although impairment of baseline motor performance was relatively mild, the ability to adapt the phase of the vestibulo-ocular reflex and to consolidate gain adaptations was strongly compromised. Purkinje cells showed abnormal patterns of simple spikes, both during and in the absence of evoked compensatory eye movements. On the basis of modeling our experimental data, we propose that feedforward inhibition, by controlling the fine-scale patterns of Purkinje cell activity, enables the induction of plasticity in neurons of the cerebellar and vestibular nuclei.
Wulff
Peer
P
Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, UK.
Schonewille
Martijn
M
Renzi
Massimiliano
M
Viltono
Laura
L
Sassoè-Pognetto
Marco
M
Badura
Aleksandra
A
Gao
Zhenyu
Z
Hoebeek
Freek E
FE
van Dorp
Stijn
S
Wisden
William
W
Farrant
Mark
M
De Zeeuw
Chris I
CI
D000200:Action Potentials / Q000502:physiology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000502:physiology; D007858:Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D011963:Receptors, GABA-A / Q000235:genetics; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D014726:Vestibular Nuclei / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid