| Summary: | During embryonic activity‐dependent brain circuit refinement, neurons receiving the same natural sensory input may undergo either long‐term potentiation (LTP) or depression (LTD). While the origin of variable plasticity in vivo is unknown, the type of plasticity induced plays a key role in shaping dynamic neural circuit synaptogenesis and growth. Here, we investigate the effects of natural visual stimuli on functional neuronal firing within the intact and awake developing brain using calcium imaging of 100s of central neurons in the Xenopus retinotectal system. We find that specific patterns of visual stimuli shift population responses towards either potentiation or depression in an N‐methyl‐D‐aspartate receptor (NMDAR)‐dependent manner. In agreement with the Bienenstock‐Cooper‐Munro (BCM) theory, our results show that functional potentiation or depression in individual neurons can be predicted by their specific receptive field properties and endogenous firing rates prior to plasticity induction. Enhancing pre‐training activity shifts plasticity outcomes as predicted by BCM, and this induced metaplasticity is also NMDAR dependent. Furthermore, network analysis reveals an increase in correlated firing of neurons that undergo potentiation. These findings implicate metaplasticity as a natural property governing experience‐dependent refinement of nascent embryonic brain circuits. === Medicine, Faculty of === Graduate
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