Theoretical analysis of a synaptotropic dendrite growth mechanism

It is generally believed that the genome cannot encode explicit instructions to form each synaptic connection in the nervous system, but may provide general neurite growth mechanisms which will result in proper connectivity. Recent in vivo imaging has provided evidence for a synaptotropic growth mechanism, wherein synapses could influence dendrite growth by selectively stabilizing filopodia upon which they form. We undertook a theoretical investigation into the consequences of such a growth process. Discrete stochastic simulations demonstrate that the synaptotropic mechanism can result in decreased dendritic wiring length, is capable of searching for regions of high density pre-synaptic partners, and can recapitulate specific patterns of dendrite growth and connectivity. A mean-field analysis shows that growth by selective stabilization of filopodia can be approximated as a reaction-diffusion system, with a spatially varying diffusion constant that depends on the probability of synapse formation. Thus, growth will occur faster in regions of appropriate synaptic connections, and the net growth can be shown to climb a gradient of synaptic partner density. Synaptotropic growth thus presents a mechanism for the emergent development of connectivity based on local properties of the circuit elements, rather than explicit dependence on global guidance molecules or innate predetermined branching programs.