Spike-Timing Dependence of Structural Plasticity Explains Cooperative Synapse Formation in the Neocortex

Structural plasticity governs the long-term development of synaptic connections in the neocortex. While the underlying processes at the synapses are not fully understood, there is strong evidence that a process of random, independent formation and pruning of excitatory synapses can be ruled out. Instead, there must be some cooperation between the synaptic contacts connecting a single pre- and postsynaptic neuron pair. So far, the mechanism of cooperation is not known. Here we demonstrate that local correlation detection at the postsynaptic dendritic spine suffices to explain the synaptic cooperation effect, without assuming any hypothetical direct interaction pathway between the synaptic contacts. Candidate biomolecular mechanisms for dendritic correlation detection have been identified previously, as well as for structural plasticity based thereon. By analyzing and fitting of a simple model, we show that spike-timing correlation dependent structural plasticity, without additional mechanisms of cross-synapse interaction, can reproduce the experimentally observed distributions of numbers of synaptic contacts between pairs of neurons in the neocortex. Furthermore, the model yields a first explanation for the existence of both transient and persistent dendritic spines and allows to make predictions for future experiments. Author Summary: Structural plasticity has been observed even in the adult mammalian neocortex – in seemingly static neuronal circuits structural remodeling is continuously at work. Still, it has been shown that the connection patterns between pairs of neurons are not random. In contrast, there is evidence that the synaptic contacts between a pair of neurons cooperate: several experimental studies report either zero or about 3–6 synapses between neuron pairs. The mechanism by which the synapses cooperate, however, has not yet been identified. Here we propose a model for structural plasticity that relies on local processes at the dendritic spine. We combine and extend the previous models and determine the equilibrium probability distribution of synaptic contact numbers of the model. By optimizing the parameters numerically for each of three reference datasets, we obtain equilibrium contact number distributions that fit the references very well. We conclude that the local dendritic mechanisms that we assume suffice to explain the cooperative synapse formation in the neocortex.