Commentary
Nonsynaptic diffusion neurotransmission (NDN) in the brain

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Abstract

The synapse has dominated the conceptual model of neurotransmission; other mechanisms, such as neuromodulation, have been considered to support and complement synaptic transmission. In this commentary, the conceptual framework considers synaptic transmission as one of several mechanisms of neurotransmission. One of these is nonsynaptic diffusion neurotransmission (NDN), which includes both the diffusion of neurotransmitters and other neuroactive substances through the extracellular fluid to reach extrasynaptic receptors, and the diffusion of substances such as nitric oxide through both the extracellular fluid and cellular membranes to act within the cell. The possible roles of NDN in mass, sustained functions such as mood, sleep and brain “tone”, as well as in various other functions, such as in long term potentiation, at the retinal, lateral geniculate nucleus and visual cortex levels of the visual system, in recovery from brain damage and in neuropharmacology, are explored.

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      Among the range of functions in which volume transmission plays a role are many of those mediated by noradrenaline.11 Volume transmission may be the primary information transmission mechanism in several abnormal functions, such as mood disorders, spinal shock, spasticity, shoulder-hand and autonomic dysreflexia syndromes, pain, and drug addiction.18,28–30 Work performed in the Routtenberg Laboratory31 in the late 1960s suggested that transmitters could readily move in the extracellular space (the fluid that surrounds neurons in the brain) and travel over distances by directional flow.

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