Synaptic plasticity is the cellular basis underlying learning and memory, and its direction is thought to determine the direction of learning and memory, acquisition or extinction. Although many signaling molecules involved in various types of synaptic plasticity have been identified so far, signaling mechanism to determine the direction of synaptic plasticity has not been fully understood.
The parallel fiber (PF) to Purkinje cell (PC) synapse (PF synapse) in the cerebellum shows two types of plasticity, long-term depression (PF-LTD) and long-term potentiation (PF-LTP). Previous studies including those from our group indicate PF-LTD is the cellular basis for acquisition of motor learning (e.g. eyeblink conditioning (EBC) and optokinetic response), whereas PF-LTP is essential for extinction of EBC. In this symposium, I will introduce our resent researches demonstrating involvement of reactive oxygen species (ROS) signaling in determination of the direction of cerebellar synaptic plasticity. ROS is involved in PF-LTD through the activation of protein kinase G (PKG) signaling. It also impairs signaling cascade essential for PF-LTP and ensures induction of PF-LTD. Our studies indicate that dual role of ROS determines the direction of cerebellar synaptic plasticity and cerebellar-dependent motor learning.