Gallimore, Andrew R. Kim, Taegon Tanaka-Yamamoto, Keiko De Schutter, Erik 2024-01-19T23:33:05Z 2024-01-19T23:33:05Z 2021-09-03 2018-01-16 2211-1247 https://pubs.kist.re.kr/handle/201004/121802 Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold. However, if the calcium signal surpasses the threshold for CaMKII activation, then an ultrasensitive "on switch'' activates an extracellular signal-regulated kinase (ERK)-based positive feedback loop that triggers LTD instead. This postsynaptic feedback loop is sustained by another, trans-synaptic, feedback loop that maintains nitric oxide production throughout LTD induction. When full depression is achieved, an automatic "off switch'' inactivates the feedback loops, returning the network to its basal state and demarcating the end of the early phase of LTD. English CELL PRESS LONG-TERM DEPRESSION AMPA RECEPTOR TRAFFICKING NITRIC-OXIDE SYNTHASE PURKINJE CELL SYNAPSES PROTEIN-KINASE-II SYNAPTIC DEPRESSION CANNABINOID RECEPTORS MEDIATED ENDOCYTOSIS SIGNAL-TRANSDUCTION SURFACE EXPRESSION Switching On Depression and Potentiation in the Cerebellum Article 10.1016/j.celrep.2017.12.084 1 CELL REPORTS, v.22, no.3, pp.722 - 733 CELL REPORTS 22 3 722 733 scie scopus 000423449400013 2-s2.0-85041640184 Cell Biology Cell Biology Article LONG-TERM DEPRESSION AMPA RECEPTOR TRAFFICKING NITRIC-OXIDE SYNTHASE PURKINJE CELL SYNAPSES PROTEIN-KINASE-II SYNAPTIC DEPRESSION CANNABINOID RECEPTORS MEDIATED ENDOCYTOSIS SIGNAL-TRANSDUCTION SURFACE EXPRESSION CaMKII cerebellum LTD LTP nitric oxide NSF PKC plasticity Purkinje cell ultrasensitivity