The Missing Piece in the "Use It or Lose It" Puzzle: Is Inhibition Regulated by Activity or Does it Act on its Own Accord?

Abstract

We have gained enormous insight into the mechanisms underlying both activity-dependent and (to a lesser degree) -independent plasticity of excitatory synapses. Recently, cortical inhibition has been shown to play a vital role in the formation of critical periods for sensory plasticity. As such, sculpting of neuronal circuits by inhibition may be a common mechanism by which activity organizes or reorganizes brain circuits. Disturbances in the balance of excitation and inhibition in the neocortex provoke abnormal activities, such as epileptic seizures and abnormal cortical development. However, both the process of experience-dependent postnatal maturation of neocortical inhibitory networks and its underlying mechanisms remain elusive. Mechanisms that match excitation and inhibition are central to achieving balanced function at the level of individual circuits. The goal of this review is to reinforce our understanding of the mechanisms by which developing inhibitory networks are able to adapt to sensory inputs, and to maintain their balance with developing excitatory networks. Discussion is centered on the following questions related to experience-dependent plasticity of neocortical inhibitory networks: 1) What are the roles of GABAergic inhibition in the postnatal maturation of neocortical circuits? 2) Does the maturation of neocortical inhibitory circuits proceed in an activity-dependent manner or do they develop independently of sensory inputs? 3) Does activity regulate inhibitory networks in the same way it regulates excitatory networks? 4) What are the molecular and cellular mechanisms that underlie the activity-dependent maturation of inhibitory networks? 5) What are the functional advantages of experience-dependent plasticity of inhibitory networks to network processing in sensory cortices?