Volume transmission in health and disease: communication via the brain extracellular space

Abstract

An important means of communication between neurons and neurons and glia is extrasynaptic ‘volume’ transmission, which is mediated by diffusion in the extracellular space (ECS). Following their release, a number of neuroactive substances, including ions, mediators, metabolites and neurotransmitters, diffuse via the ECS to targets distant from their release sites. Glial cells and the extracellular matrix affect the composition, geometry and volume of the ECS and therefore also extracellular diffusion during development, aging and pathological states such as ischaemia, injury, X‐irradiation, gliosis, demyelination and in grafted tissue. Changes in diffusion parameters affect neuron–glia communication, ionic homeostasis and the movement and accumulation of neuroactive substances and therefore play an important role in volume transmission in functions such as vigilance, sleep, depression, chronic pain, LTP, memory formation and other plastic changes in the CNS.