Asymmetries in Cerebellar Plasticity and Motor Learning

Abstract

Synaptic plasticity at the parallel fiber to Purkinje cell synapse has long been considered a cellular correlate for cerebellar motor learning. Functionally, long-term depression and long-term potentiation at these synapses seem to be the reverse of each other, with both pre- and post-synaptic expression occurring in both. However, different cerebellar motor learning paradigms have been shown to be asymmetric and not equally reversible. Here, we discuss the asymmetric reversibility shown in the vestibulo-ocular reflex and eyeblink conditioning and suggest that different cellular plasticity mechanisms might be recruited under different conditions leading to unequal reversibility.

Keywords: Cerebellum; Eyeblink conditioning; Motor learning; Purkinje cells; Synaptic plasticity; Vestibulo-ocular reflex.

Figure 1

Post-synaptic LTP and LTD are completely reversible in cerebellar slices, yet cerebellar learning in the VOR shows pronounced asymmetry. a: Post-synaptic LTD can completely reverse prior post-synaptic LTP. Time graph showing 1 Hz LTP (PF stimulation) followed by LTD (PF+CF). Arrows indicate the time points of tetanization. Error bars are mean ± SEM. Panel (a) is taken from Coesmans et al (2004). Copyright 2004 by Elsevier. b and c: In naïve cats, gain-down learning limited subsequent gain-up learning. b: Time course of VOR gain, measured at 0.5 Hz, over 2–3 hours in cats wearing magnifying (x2) or miniaturizing (x0.25) lenses. In the “up-up” and “down-down” protocol, cats wore the magnifying or miniaturizing lenses for 2 hours. In the “up-down-down” and “down-up-up” protocols the lenses were switched after the first hour. c: Summary of final gain change from panel B. In the down-up-up protocol, 2 hours of gain up learning failed to increase the VOR gain above pre-learning values. Panels (b) and (c) are modified from Broussard et al. (2011). Copyright 2011 by Springer.