Joanna Jędrzejewska‐Szmek, Sriraman Damodaran, Daniel B. Dorman, Kim T. Blackwell

The striatum is a major site of learning and memory formation for sensorimotor and cognitive association. One of the mechanisms used by the brain for memory storage is synaptic plasticity - the long lasting, activity-dependent change in synaptic strength. All forms of synaptic plasticity require an elevation in intracellular calcium, and a common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity. The utility of this hypothesis in the striatum is unclear in part because dopamine is required for striatal plasticity and in part because of the diversity in stimulation protocols. To test whether calcium can predict plasticity direction, we developed a calcium-based plasticity rule using a spiny projection neuron model with sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion. We utilize three spike-timing-dependent plasticity (STDP) induction protocols, in which post-synaptic potentials are paired with precisely timed action potentials and the timing of such pairing determines whether potentiation or depression will occur. Results show that despite the variation in calcium dynamics, a single, calcium-based plasticity rule, which explicitly considers duration of calcium elevations, can explain the direction of synaptic weight change for all three STDP protocols. Additional simulations show that the plasticity rule correctly predicts the NMDA receptor dependence of long-term potentiation and the L-type channel dependence of long term depression. By utilizing realistic calcium dynamics, the model reveals mechanisms controlling synaptic plasticity direction, and shows that the dynamics of calcium, not just calcium amplitude, are crucial for synaptic plasticity. This article is protected by copyright. All rights reserved.