@article {SakuraiENEURO.0056-16.2016, author = {Akira Sakurai and Arianna N. Tamvacakis and Paul S. Katz}, title = {Recruitment of polysynaptic connections underlies functional recovery of a neural circuit after lesion}, elocation-id = {ENEURO.0056-16.2016}, year = {2016}, doi = {10.1523/ENEURO.0056-16.2016}, publisher = {Society for Neuroscience}, abstract = {Recruitment of additional neurons to neural circuits often occurs in accordance with changing functional demands. Here we found that synaptic recruitment plays a key role in functional recovery after neural injury. Disconnection of a brain commissure in the nudibranch mollusc, Tritonia diomedea, impairs swimming behavior by eliminating particular synapses in the CPG underlying the rhythmic swim motor pattern. However, the CPG functionally recovers within a day after the lesion. The strength of a spared inhibitory synapse within the CPG from Cerebral Neuron 2 (C2) to Ventral Swim Interneuron B (VSI), determines the level of impairment caused by the lesion, which varies among individuals. In addition to this direct synaptic connection, there are polysynaptic connections from C2 and Dorsal Swim Interneurons (DSIs) to VSI that provide indirect excitatory drive but play only minor roles under normal conditions. After disconnecting the pedal commissure (PdN6), recruitment of polysynaptic excitation became a major source of excitatory drive to VSI. Moreover, the amount of polysynaptic recruitment, which changed over time, differed among individuals and correlated with the degree of recovery of the swim motor pattern. Thus, functional recovery was mediated by an increase in the magnitude of polysynaptic excitatory drive, compensating for the loss of direct excitation. Since the degree of susceptibility to injury corresponds to existing individual variation in the C2 to VSI synapse, the recovery relied upon the extent to which the network reorganized to incorporate additional synapses.Significance Statement: In cases of permanent neuronal injury, functional recovery can occur through reorganization of the remaining neural circuitry. Here, this study shows that a molluscan neural circuit recruits additional neurons in response to a lesion and that the extent of recruitment predicts the extent of behavioral recovery. Interestingly, the initial susceptibility of the circuit to this lesion reflects the strength of a specific synapse within the circuit, but the functional recovery correlates with polysynaptic recruitment from outside the canonical motor circuit. Thus, even in a well-defined invertebrate neural circuit, there are indirect, polysynaptic pathways that provide compensatory function or flexibility to the circuit. Such individual variability appears to be hidden under normal conditions but becomes relevant when challenged by neural injury.}, URL = {https://www.eneuro.org/content/early/2016/07/25/ENEURO.0056-16.2016}, eprint = {https://www.eneuro.org/content/early/2016/07/25/ENEURO.0056-16.2016.full.pdf}, journal = {eNeuro} }