Long-term depression (LTD) at parallel fiber (PF) to Purkinje cell (PC) synapses has been considered as a main cellular mechanism for motor learning. However, the necessity of LTD for motor learning was challenged by demonstration of normal motor learning in the LTD-defective animals. Here, we addressed possible involvement of LTD in motor learning by examining whether LTD occurs during motor learning in the wild-type mice. As a model of motor learning, adaptation of optokinetic response (OKR) was used. OKR is a type of reflex eye movement to suppress blur of visual image during animal motion. OKR shows adaptive change during continuous optokinetic stimulation, which is regulated by the cerebellar flocculus. After OKR adaptation, amplitudes of quantal excitatory postsynaptic currents at PF-PC synapses were decreased, and induction of LTD was suppressed in the flocculus. These results suggest that LTD occurs at PF-PC synapses during OKR adaptation.

Norepinephrine modulates synaptic plasticity in various brain regions and is implicated in memory formation, consolidation and retrieval. The cerebellum is involved in motor learning, and adaptations of the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) have been studied as models of cerebellum-dependent motor learning. Previous studies showed the involvement of adrenergic systems in the regulation of VOR, OKR and cerebellar synaptic functions. Here, we show differential contributions of β- and α2-adrenergic receptors in the mouse cerebellar flocculus to VOR and OKR control. Effects of application of β- or α2-adrenergic agonist or antagonist into the flocculus suggest that the β-adrenergic receptor activity maintains the VOR gain at high levels and contributes to adaptation of OKR, and that α2-adrenergic receptor counteracts the β-receptor activity in VOR and OKR control. We also examined effects of norepinephrine application, and the results suggest that norepinephrine regulates VOR and OKR through β-adrenergic receptor at low concentrations and through α2-receptor at high concentrations.

No abstract

No abstract

No abstract