Artificial Synaptic Rewiring Demonstrates that Distinct Neural Circuit Configurations Underlie Homologous Behaviors.

Behavioral homology is often assumed to involve similarity in underlying neuronal mechanisms. Here, we provide a counterexample where homologous behaviors are produced by neurons with different synaptic connectivity. The nudibranch molluscs Melibe leonina and Dendronotus iris exhibit homologous swimming behaviors, consisting of alternating left and right body flexions. The swim central pattern generators (CPGs) in both species are composed of bilaterally symmetric interneurons, which are individually identified and reciprocally inhibit their contralateral counterparts, contributing to left-right burst alternation in the swim motor patterns. In Melibe, the swim CPG contains two parts that interact to produce stable rhythmic bursting; one part is the primary half-center kernel, and the other part, which consists of a bilateral pair of neurons called Si3, regulates period length. The Dendronotus swim CPG is simpler, with Si3 being part of the primary half-center oscillator. Application of curare (d-tubocurarine) selectively blocked the Si3 synapses in both species. In Melibe, curare application caused the burst duration of the swim motor pattern to lengthen, whereas in Dendronotus, curare halted bursting altogether. In both species, replacing the curare-blocked Si3 synapses with artificial synapses using dynamic clamp restored the original rhythmic bursting, thereby affirming the roles of those synapses. The curare-impaired bursting in Dendronotus was also restored by rewiring the homologous neurons into a Melibe-like primary half-center oscillator configuration, indicating that the connectivity itself could account for species differences in circuit responses to curare. The results suggest that synaptic connectivity diverged during evolution while behavior was conserved.