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Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities


Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities

Louis-Eric Trudeau et al. Front Neural Circuits.


Multiple discoveries made since the identification of vesicular glutamate transporters (VGLUTs) two decades ago revealed that many neuronal populations in the brain use glutamate in addition to their "primary" neurotransmitter. Such a mode of cotransmission has been detected in dopamine (DA), acetylcholine (ACh), serotonin (5-HT), norepinephrine (NE) and surprisingly even in GABA neurons. Interestingly, work performed by multiple groups during the past decade suggests that the use of glutamate as a cotransmitter takes different forms in these different populations of neurons. In the present review, we will provide an overview of glutamate cotransmission in these different classes of neurons, highlighting puzzling differences in: (1) the proportion of such neurons expressing a VGLUT in different brain regions and at different stages of development; (2) the sub-cellular localization of the VGLUT; (3) the localization of the VGLUT in relation to the neurons' other vesicular transporter; and (4) the functional role of glutamate cotransmission.

Keywords: VGLUT; cotransmission; glutamate; synapse; vesicular transporters.


Figure 1
Figure 1
The co-expression of two vesicular neurotransmitter transporters by a single neuron generates multiple signaling possibilities. (A,B) Two different vesicular neurotransmitter transporters (VNT1 or VNT2) can either be addressed to the same synaptic vesicles (SVs) or segregated in different SVs. In the first case the two transmitters (NT1 and NT2) will be coreleased simultaneously, in the second one they can be differentially released. (C) Within a neuron, two different VNTs can be targeted the same or to different varicosities. With these two options, a neuron can release two different NTs from various varicosities or corelease two NTs from a single varicosity.

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