Glial cells and volume transmission in the CNS

Although synaptic transmission is an important means of communication betwe en neurons, neurons themselves and neurons and glia also communicate by ext rasynaptic "volume" transmission, which is mediated by diffusion in the ext racellular space (ECS). The ECS of the central nervous system (CNS) is the microenvironment of neurons and glial cells. The composition and size of EC S change dynamically during neuronal activity as well as during pathologica l states. Following their release, a number of neuroactive substances, incl uding ions, mediators, metabolites and neurotransmitters, diffuse via the E CS to targets distant from their release sites. Glial cells affect the comp osition and volume of the ECS and therefore also extracellular diffusion, p articularly during development, aging and pathological states such as ische mia, injury, X-irradiation, gliosis, demyelination and often in grafted tis sue. Recent studies also indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g. in the vicinity of oligodendrocytes. Besides glial cells, the extracellular matrix also changes ECS geometry and forms diffus ion barriers, which may also result in diffusion anisotropy. Glial cells th erefore play an important role in extrasynaptic transmission, for example i n functions such as vigilance, sleep, depression, chronic pain, LTP, LTD, m emory formation and other plastic changes in the CNS. In turn, ECS diffusio n parameters affect neuron-glia communication, ionic homeostasis and moveme nt and/or accumulation of neuroactive substances in the brain. (C) 2000 Els evier Science Ltd. All rights reserved.