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      Extrasynaptic exocytosis and its mechanisms: a source of molecules mediating volume transmission in the nervous system

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          We review the evidence of exocytosis from extrasynaptic sites in the soma, dendrites, and axonal varicosities of central and peripheral neurons of vertebrates and invertebrates, with emphasis on somatic exocytosis, and how it contributes to signaling in the nervous system. The finding of secretory vesicles in extrasynaptic sites of neurons, the presence of signaling molecules (namely transmitters or peptides) in the extracellular space outside synaptic clefts, and the mismatch between exocytosis sites and the location of receptors for these molecules in neurons and glial cells, have long suggested that in addition to synaptic communication, transmitters are released, and act extrasynaptically. The catalog of these molecules includes low molecular weight transmitters such as monoamines, acetylcholine, glutamate, gama-aminobutiric acid (GABA), adenosine-5-triphosphate (ATP), and a list of peptides including substance P, brain-derived neurotrophic factor (BDNF), and oxytocin. By comparing the mechanisms of extrasynaptic exocytosis of different signaling molecules by various neuron types we show that it is a widespread mechanism for communication in the nervous system that uses certain common mechanisms, which are different from those of synaptic exocytosis but similar to those of exocytosis from excitable endocrine cells. Somatic exocytosis has been measured directly in different neuron types. It starts after high-frequency electrical activity or long experimental depolarizations and may continue for several minutes after the end of stimulation. Activation of L-type calcium channels, calcium release from intracellular stores and vesicle transport towards the plasma membrane couple excitation and exocytosis from small clear or large dense core vesicles in release sites lacking postsynaptic counterparts. The presence of synaptic and extrasynaptic exocytosis endows individual neurons with a wide variety of time- and space-dependent communication possibilities. Extrasynaptic exocytosis may be the major source of signaling molecules producing volume transmission and by doing so may be part of a long duration signaling mode in the nervous system.

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          Interneurons of the hippocampus.

            • Record: found
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            Structure and function of the brain serotonin system.

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              • Article: not found

              Prefrontal acetylcholine release controls cue detection on multiple timescales.

              Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.

                Author and article information

                Front Physiol
                Front Physiol
                Front. Physio.
                Frontiers in Physiology
                Frontiers Media S.A.
                02 May 2012
                04 September 2012
                : 3
                1Departamento de Neurofisiología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz México, D.F., México
                2Instituto de Fisiología Celular, Universidad Nacional Autónoma de México México, D.F., México
                Author notes

                Edited by: Kjell Fuxe, Karolinska Institutet, Sweden

                Reviewed by: Kjell Fuxe, Karolinska Institutet, Sweden; A. Del Arco, Universidad Complutense de Madrid, Spain

                *Correspondence: Citlali Trueta, Departamento de Neurofisiología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Tlalpan 14370, México, D.F., México. e-mail: ctrueta@ 123456imp.edu.mx

                This article was submitted to Frontiers in Membrane Physiology and Biophysics, a specialty of Frontiers in Physiology.

                Copyright © 2012 Trueta and De-Miguel.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 263, Pages: 19, Words: 18020
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