Norepinephrine Facilitates Induction of Long-term Depression through β-Adrenergic Receptor at Parallel Fiber-to-Purkinje Cell Synapses in the Flocculus

Abstract

The cerebellum is involved in motor learning, and long-term depression (LTD) at parallel fiber-to-Purkinje cell (PF-PC) synapses has been considered to be a primary cellular mechanism for motor learning. In addition, the contribution of norepinephrine (NE) to cerebellum-dependent learning paradigms has been reported. Thus, the roles of LTD and of NE in motor learning have been studied separately, and the relationship between the effects of NE and LTD remains unclear. Here, we examined effects of β-adrenergic receptor (β-AR) activity on the synaptic transmission and LTD at PF-PC synapses in the cerebellar flocculus. The flocculus regulates adaptation of oculomotor reflexes, and we previously reported the involvement of both LTD and β-AR in adaptation of an oculomotor reflex. Here we found that specific agonists for β-AR or NE did not directly change synaptic transmission, but lowered the threshold for LTD induction at PF-PC synapses in the flocculus. In addition, protein kinase A (PKA), which is activated downstream of β-AR, facilitated the LTD induction. Altogether, these results suggest that NE facilitates LTD induction at PF-PC synapses in the flocculus by activating PKA through β-AR.