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• W2003168086 abstract "The predominance of dopamine (DA) receptors at extrasynaptic vs. synaptic sites implies that DA signaling is by diffusion-based volume transmission. In this review, we compare characteristics that regulate extracellular DA behavior in substantia nigra pars compacta (SNc) and striatum, including regional differences in structure (a 40% greater extracellular volume fraction in SNc vs. striatum) and in dynamic DA uptake (a 200-fold greater DA uptake rate in striatum vs. SNc). Furthermore, we test the assumption of diffusion-based volume transmission for SNc and striatum by modeling dynamic DA behavior after quantal release using region-specific parameters for diffusion and uptake at 37 °C. Our model shows that DA uptake does not affect peak DA concentration within 1 μm of a release site in either SNc or striatum because of the slow kinetics of DATs vs. diffusion. Rather, diffusion and dilution are the dominant factors governing DA concentration after quantal release. In SNc, limited DAT efficacy is reflected in a lack of influence of uptake on either amplitude or time course of DA transients after quantal release up to 10 μm from a release site. In striatum, the lack of effect of the DAT within 1 μm of a release site means that perisynaptic DATs do not “gate” synaptic spillover. This contrasts with the conventional view of DA synapses, in which DATs efficiently recycle DA by re-uptake into the releasing axon terminal. However, the model also shows that a primary effect of striatal uptake is to curtail DA lifetime after release. In both SNc and striatum, effective DA radius after quantal release is ~ 2 μm for activation of low-affinity DA receptors and 7–8 μm for high-affinity receptors; the corresponding spheres of influence would encompass tens to thousands of synapses. Thus, the primary mode of intercellular communication by DA, regardless of region, is volume transmission." @default.
• W2003168086 created "2016-06-24" @default.
• W2003168086 creator A5043025373 @default.
• W2003168086 creator A5087084011 @default.
• W2003168086 date "2008-08-01" @default.
• W2003168086 modified "2023-10-12" @default.
• W2003168086 title "Dopamine spillover after quantal release: Rethinking dopamine transmission in the nigrostriatal pathway" @default.
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• W2003168086 doi "https://doi.org/10.1016/j.brainresrev.2008.02.004" @default.
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