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Cell Rep. 2018 Jan 16;22(3):722-733. doi: 10.1016/j.celrep.2017.12.084.

Switching On Depression and Potentiation in the Cerebellum.

Author information

1
Computational Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan. Electronic address: andrew.gallimore@oist.jp.
2
Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
3
Computational Neuroscience Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan. Electronic address: erik@oist.jp.

Abstract

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.

KEYWORDS:

CaMKII; LTD; LTP; NSF; PKC; Purkinje cell; cerebellum; nitric oxide; plasticity; ultrasensitivity

PMID:
29346769
DOI:
10.1016/j.celrep.2017.12.084
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