Adaptive control of synaptic plasticity integrates micro- and macroscopic network function.

Synaptic plasticity configures interactions between neurons and is therefore likely to be a primary driver of behavioral learning and development. How this microscopic-macroscopic interaction occurs is poorly understood, as researchers frequently examine models within particular ranges of abstraction and scale. Computational neuroscience and machine learning models offer theoretically powerful analyses of plasticity in neural networks, but results are often siloed and only coarsely linked to biology. In this review, we examine connections between these areas, asking how network computations change as a function of diverse features of plasticity and vice versa. We review how plasticity can be controlled at synapses by calcium dynamics and neuromodulatory signals, the manifestation of these changes in networks, and their impacts in specialized circuits. We conclude that metaplasticity-defined broadly as the adaptive control of plasticity-forges connections across scales by governing what groups of synapses can and can't learn about, when, and to what ends. The metaplasticity we discuss acts by co-opting Hebbian mechanisms, shifting network properties, and routing activity within and across brain systems. Asking how these operations can go awry should also be useful for understanding pathology, which we address in the context of autism, schizophrenia and Parkinson's disease.