Neurotransmission in the brain by diffusion through the extracellular fluid: a review.

Synaptic or 'hard wired' neurotransmission in the brain, subject to modulation by a class of substances called modulators, has been the dominant model of brain function. However, increasing evidence for alternate non-synaptic neurotransmission mechanisms is forcing consideration of a more inclusive model. Evidence is presented for such neurotransmitter systems that require diffusion through the extracellular fluid. Old and new findings have been interpreted within a conceptual framework that is not centered on the synaptic model, but instead considers a continuum of neurotransmitter actions.