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

cerebellum is involved in motor learning, and long-term depression (LTD) at parallel fiber-toPurkinje 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 p-adrenergic receptor (p-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 p-AR in adaptation of an oculomotor reflex. Here we found that specific agonists for p-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 p-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 p-AR. This article is part of a Special Issue entitled: In Memoriam: Masao Ito?A Visionary Neuroscientist with a Passion for the Cerebellum. ? 2020 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

The cerebellum is involved in motor learning, with LTD at PF-PC synapses considered a primary mechanism. NE's contribution to cerebellum-dependent learning has been reported separately. Studies have found that NE facilitates LTD induction at PF-PC synapses in the cerebellar flocculus through activation of PKA via p-AR.