Emerging roles of metaplasticity in behaviour and disease.

Since its initial conceptualisation, metaplasticity has come to encompass a wide variety of phenomena and mechanisms, creating the important challenge of understanding how they contribute to network function and behaviour. Here, we present a framework for considering potential roles of metaplasticity across three domains of function. First, metaplasticity appears ideally placed to prepare for subsequent learning by either enhancing learning ability generally or by preparing neuronal networks to encode specific content. Second, metaplasticity can homeostatically regulate synaptic plasticity, and this likely has important behavioural consequences by stabilising synaptic weights while ensuring the ongoing availability of synaptic plasticity. Finally, we discuss emerging evidence that metaplasticity mechanisms may play a role in disease causally and may serve as a potential therapeutic target.