Reevaluating the Role of LTD in Cerebellar Motor Learning

SummaryLong-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.

► Motor learning is tested in three mutant mouse models lacking PF-PC LTD expression ► VOR and OKR short-term gain adaptation are not affected in mutants lacking LTD ► VOR phase reversal is not impaired in mutants or in controls after chemical LTD block ► Eyeblink conditioning and Erasmus Ladder learning are also not affected in mutants