Meier, R. J.; Muller, S. Z.; Wang, B.; Mizerska, K.; Jain, S.; Fothergill, T.; Mercer, J.; Klapheke, C.; DiSano, J.; Milicic, N.; Wang, R.; Narayan, S.; Li, J.; Weiss, K.; Alvarez-Salvado, E.; Ahrens, M. B.; Hibi, M.; Huisken, J.; Eliceiri, K. W.; Ehrlich, D. E.

Synaptic plasticity is often guided by instructive inputs to neural circuits, but learning only succeeds when these instructions reach neurons that mediate relevant outputs. This creates the credit assignment problem: how does a neuron receive instructions suited to its own behavioral function? Here we report a developmental mechanism that enables credit assignment by using instructive inputs to organize the downstream architecture through which learning is expressed. In the olivocerebellar learning system, the inferior olive provides instructive inputs that guide plasticity within the cerebellum. During circuit assembly in zebrafish, we find these same inputs regulate long-range cerebellar projections during a highly plastic, two-day critical period. Developmental experience caused specific maturation of projections to targets that were coactivated with olivary inputs. Mathematical theory and computational modeling show how the resulting architecture constrains later learning, such that a single input can sculpt downstream connectivity and then leverage that circuit to assign credit. Simulated learning became paradoxically more robust if we reduced plasticity after a developmental critical period, protecting key architecture from corruption during learning. Thus, instructive inputs can first build the circuits they later teach, coordinating development and learning to enable effective credit assignment.