Calcium-based input timing learning

A bstract Stimulus-triggered synaptic long-term plasticity is the foundation of learning and other cognitive abilities of the brain. In general, long-term synaptic plasticity is subdivided into two different forms: homosynaptic plasticity describes synaptic changes at stimulated synapses, while heterosynaptic plasticity summarizes synaptic changes at non-stimulated synapses. For homosynaptic plasticity, the Ca 2+ -hypothesis pinpoints the calcium concentration within a stimulated dendritic spine as key mediator or controller of underlying biochemical and -physical processes. On the other hand, for heterosynaptic plasticity, although theoretical studies attribute important functional roles to it, such as synaptic competition and cooperation, experimental results remain ambiguous regarding its manifestation and biological basis. By integrating insights from Ca 2+ -dependent homosynaptic plasticity with experimental data of dendritic Ca 2+ -dynamics, we developed a mathematical model that describes the complex temporal and spatial dynamics of calcium in dendrites.We show that the influx of calcium into a stimulated spine can lead to its diffusion to neighboring spines, triggering heterosynaptic effects such as synaptic competition or cooperation. By considering different input strengths, our model explains the ambiguity of reported experimental results of heterosynaptic plasticity, suggesting that the Ca 2+ -hypothesis of homosynaptic plasticity can be extended to also model heterosynaptic plasticity. Furthermore, our model predicts thata synapse can modulate the expression of homosynaptic plasticity at a neighboring synapse in an input-timing-dependent manner, without the need of postsynaptic spiking. The resulting sensitivity of synaptic plasticity on input-spike-timing can be influenced by the distance between involved spines as well as the local diffusion properties of the connecting dendritic shaft, providing a new way of dendritic computation.