Figure 1. Cerebellar Circuitry, Basic Motor Performance, and Short-Term Motor Learning.

(A) The vestibulo-cerebellum receives excitatory input from the inferior olive (IO, orange) and vestibular ganglion cells (VG, green) and sends an inhibitory projection (black) back to the cerebellar and vestibular nuclei (CN/VN), and from there onward to motor nuclei (MN). According to the Marr-Albus-Ito hypothesis, the climbing fibers (CF) originating in the IO carry the error signal and the mossy fiber-parallel fiber system (MF-PF) relays motor activity signals. The inset shows how, after concomitant activity in CF and PF, AMPA receptors are internalized through interaction of PICK1 (red) with the C-terminal region of AMPA-type glutamate receptor subunit GluR2 (dark gray), resulting in LTD of the PF to Purkinje cell synapse (PF-PC LTD). In the mutant mice used herein, PF-PC LTD expression is blocked either by deletion of PICK1, a knockin in which GluR2 is replaced with a truncated form involving deletion of the last seven amino acids of GluR2 (GluR2Δ7; blue), or within a knockin harboring a point mutation in the PKC recognition motif of GluR2 (GluR2K882A; green). (B) Gain values of the PICK1 KO, GluR2Δ7 KI, and GluR2K882A KI mutants during the optokinetic reflex (OKR), vestibulo-ocular reflex (VOR) in the dark, and VVOR are not significantly different from those of wild-type controls (black). (C) Short-term visuo-vestibular, out-of-phase mismatch training resulted in significant (p < 0.005 for all groups) gain increases of PICK1 KO, GluR2Δ7 KI, and GluR2K882A KI mutants during the OKR (top panel) and VOR (bottom panel). Short-term visuo-vestibular, in-phase mismatch training resulted in significant (p < 0.001 for all groups) gain decreases of PICK1 KO, GluR2Δ7 KI, and GluR2K882A KI mutants during the VOR (middle panel). All these changes were not significantly different from those of wild-type controls. For clarity of presentation the wild-types are presented as a pooled group. For number of mice per group, see Table S1. The p values for individual mutants versus all controls and versus littermates are listed in Table S2. Error bars denote SEM.