Developmental time windows for axon growth influence neuronal network topology

TL;DR

This study investigates how the timing of axon growth during early brain development affects the topology and spatial organization of neuronal networks, revealing distinct properties based on growth timing patterns.

Contribution

It introduces a comparative analysis of parallel versus serial axon growth timing and their impact on network topology, supported by empirical data from C. elegans.

Findings

Serial growth leads to higher out-degrees and local efficiency.

Parallel growth results in more homogeneous connectivity and more bidirectional connections.

Connection probability decreases faster with distance in parallel growth.

Abstract

Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation especially concerning short-distance connectivity during early development, either starting at the same time for all neurons (parallel, i.e. maximally-overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e. no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency, and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.