A generalized mathematical framework for the calcium control hypothesis describes weight-dependent synaptic...

The brain modifies synaptic strengths to store new information via long-term potentiation (LTP) and long-term depression (LTD). Evidence has mounted that long-term synaptic plasticity is controlled via concentrations of calcium ([Ca²⁺]) in postsynaptic dendritic spines. Several mathematical models describe this phenomenon, including those of Shouval, Bear, and Cooper (SBC) (Shouval et al., 2002, 2010) and Graupner and Brunel (GB) (Graupner & Brunel, 2012). Here we suggest a generalized version of the SBC and GB models, the fixed point - learning rate (FPLR) framework, where the synaptic [Ca²⁺] specifies a fixed point toward which the synaptic weight approaches asymptotically at a [Ca²⁺]-dependent rate. The FPLR framework offers a straightforward phenomenological interpretation of calcium-based plasticity: the calcium concentration tells the synaptic weight where it is going and how quickly it goes there. The FPLR framework can flexibly incorporate various experimental findings, including the existence of multiple regions of [Ca²⁺] where no plasticity occurs, or plasticity observed experimentally in cerebellar Purkinje cells, where the directionality of calcium-based synaptic changes is reversed relative to cortical and hippocampal neurons. We also suggest a modeling approach that captures the dependency of late-phase plasticity stabilization on protein synthesis. We demonstrate that due to the asymptotic nature of synaptic changes in the FPLR rule, the plastic changes induced by frequency- and spike-timing-dependent plasticity protocols are weight-dependent. Finally, we show how the FPLR framework can explain the weight-dependence observed in behavioral time scale plasticity (BTSP).