Timing dependence of the induction of cerebellar LTD

Abstract

Long-term depression (LTD) of the granule cell to Purkinje cell synapse is thought to contribute to motor learning. According to the Marr/Albus/Ito model, sensory inputs drive granule cells to fire, thereby exciting Purkinje cells and influencing motor output. Inappropriate motor output causes neurons in the inferior olive to fire and activate Purkinje cells via the powerful climbing fiber (CF) synapse. CF activity is an error signal and the association of CF and granule cell parallel fiber (PF) activity results in LTD at coactivated PF synapses. Here we examine the timing dependence of LTD by using an induction protocol consisting of a single CF activation paired with a PF burst, with the relative timing of CF and PF activation systematically varied. LTD was most prominent when PF activation occurred before CF activation. A plot of LTD magnitude as a function of PF and CF timing was well approximated by a fit in which LTD peaked for PF activity ∼80ms before CF activation and the half width was ∼300ms. This indicates that the timing dependence of LTD is well suited to allow a CF to depress preceding PF inputs that generated inappropriate motor outputs. We also find that LTD induction and endocannabinoid release have a similar dependence on PF and CF timing. This suggests that the properties of endocannabinoid release may underlie the timing dependence of some forms of motor learning.