Fig. 13.

Extracellular microenvironment and volume transmission. Upper panel. Synapses and the entire ECS are embedded in an extracellular matrix of unknown density. The extracellular matrix has several components, including lecticans, tenascin-R (TN-R), as well as tenascin-C in the developing brain, and hyaluronan (HA). G, glia; N, neuron. (Modified from Ref. 421). Lower panels. Extracellular communication. Short distance communication. This occurs via closed synapses that are typical of synaptic transmission. These synapses are often ensheathed by glial processes and by the extracellular matrix, forming perineuronal or perisynaptic nets. The ECS changes its diffusion parameters in response to neuronal activity and glial cell re-arrangement. In short-distance communication by diffusion, presynaptic terminals, postsynaptic terminals, glial cell processes and the ECS form a ‘plastic’ quadripartite synapse. Long-distance communication. The CNS architecture is composed of neurons, axons, glia, cellular processes, molecules of the extracellular matrix and intercellular channels between the cells. This architecture slows down the movement (diffusion) of substances in the brain, which is critically dependent on the ECS diffusion parameters volume fraction (α), tortuosity (λ) and in some situations, loss or uptake (k′). (Modified from Ref. 358).