Raising the Connectome: the emergence of neuronal activity and behavior in C. elegans

The differentiation of neurons and formation of connections between cells is the basis of both the adult phenotype and behaviors tied to cognition, perception, reproduction, and survival. Such behaviors are associated with local (circuits) and global (connectome) brain networks. A solid understanding of how these networks emerge is critical. This opinion piece features a guided tour of early developmental events in the emerging connectome, which is crucial to a new view on the connectogenetic process. Connectogenesis includes associating cell identities with broader functional and developmental relationships. During this process, the transition from developmental cells to terminally differentiated cells is defined by an accumulation of traits that ultimately results in neuronal-driven behavior. The well-characterized developmental and cell biology of C. elegans will be used to build a synthesis of developmental events that result in a functioning connectome. Specifically, our view of connectogenesis enables a first-mover model of synaptic connectivity to be demonstrated using data representing larval synaptogenesis. In a first-mover model of Stackleberg competition, potential pre- and postsynaptic relationships are shown to yield various strategies for establishing various types of synaptic connections. By comparing these results to what is known regarding principles for establishing complex network connectivity, these strategies are generalizable to other species and developmental systems. In conclusion, we will discuss the broader implications of this approach, as what is presented here informs an understanding of behavioral emergence and the ability to simulate related biological phenomena. HighlightsO_LIwe can understand the complexity of connectomes in terms of their emergence from embryogenetic precursors, connection dynamics, and relationship to organismal behavior. C_LIO_LIa first-mover competition model can explain how neuronal cells follow a specific set of heuristic strategies to form chemical synapses with other cells in larval development. C_LIO_LIthe timing and relative order of terminal differentiation in Caenorhabditis elegans are shown to have both subtle and consequential effects on patterns of connectivity. C_LIO_LIa correspondence is established between the emergence of small connectomes and the emergence of specific behavioral outcomes in both animal and in silico models. C_LI