Homeostatic synaptic plasticity as a metaplasticity mechanism - a molecular and cellular perspective

The molecular mechanisms underlying various types of synaptic plasticity are historically regarded as separate processes involved in independent cellular events. However, recent progress in our molecular understanding of Hebbian and homeostatic synaptic plasticity supports the observation that these two types of plasticity share common cellular events, and are often altered together in neurological diseases. Here, we discuss the emerging concept of homeostatic synaptic plasticity as a metaplasticity mechanism with a focus on cellular signaling processes that enable a direct interaction between Hebbian and homeostatic plasticity. We also identify distinct and shared molecular players involved in these cellular processes that may be explored experimentally in future studies to test the hypothesis that homeostatic synaptic plasticity serves as a metaplasticity mechanism to integrate changes in neuronal activity and support optimal Hebbian learning.