Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain

By P. Garris, E. L. Ciolkowski, Paolo Pastore, Ft. Mark Wightman. 1994

Synaptic release of dopamine in the nucleus accumbens of the intact rat brain elicited by a single electrical impulse applied to ascending dopaminergic fibers results in extracellular concentrations sufficient to bind the known dopamine receptors. The dopamine concentration observed after four rapid, sequential pulses is exactly four times greater and is unaffected by pharmacological antagonism of dopamine uptake and receptor sites at supramaximal concentrations. Thus, dopamine efflux from the synaptic cleft is not restricted by binding to intrasynaptic proteins on the time scale of the measurements (50–100 msec). The extracellular concentration, as a result of a single stimulus pulse, is 0.25 microM and is rapidly removed by extrasynaptic uptake. This maximal, transient concentration of dopamine is 60 times higher than steady-state concentrations reported previously using dialysis techniques, illustrating that dopamine extracellular concentrations are spatially and temporally heterogenous. In contrast to ACh transmission at the neuromuscular junction, the dopamine synapse in the telencephalon is designed for the effective efflux of dopamine from the synaptic cleft to the extrasynaptic compartment during neurotransmission.

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Citations in the corpus

Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. (2007, background): “The volume and time course of dopamine concentration after synaptic release has been mathematically modeled as a diffusion system with a single constant reuptake rate for the dopamine transporter (Garris et al. 1994).”
Predictive reward signal of dopamine neurons. (1998, background): “…accumbens (Wightman and Zimmerman 1990) and occurs even with Dopamine is released to 30–40% from synaptic and to 60–70% from extrasynaptic varicosities (Descarries et al.longer impulse intervals because of sparser reuptake sites (Garris et al. 1994b; Marshall et al. 1990; Stamford et al. 1996).”
A connectome of a learning and memory center in the adult Drosophila brain (2017, background): “This contrasts somewhat with dopaminergic innervation in the mammalian system, where there is typically not such close contact with a single clear post-synaptic partner, and volume transmission is the predominant model for dopamine release (Gonon, 1997; Garris et al., 1994).”
Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene (2005, background): “Spatial and temporal signaling of DA neurotransmission is controlled by the plasma membrane DAT (Amara and Kuhar, 1993; Garris et al, 1994).”
Solving the distal reward problem through linkage of STDP and dopamine signaling (2007, background): “2 s, which is greater than the experimentally measured time constant of DA uptake in striatum (around 0.1 s, Wightman and Zimmerman 1990; Garris et al. 1994) but smaller than that in the prefrontal cortex (seconds, see Cass and Gerhardt 1995).”
Multiple dopamine functions at different time courses. (2007, background): “…dorsal and ventral striatum rises within 1.3–10.0 ms from baselines of 5–10 nM via intrasynaptic peaks of 500–3000 nM to extrasynaptic concentrations of 250–500 nM in rats and guinea pigs and 500–1600 nM in monkeys (Kawagoe et al. 1992, Dugast et al. 1994, Garris et al. 1994, Cragg et al. 2000).”
Dopamine release in the basal ganglia (2011, background): “How far away from release sites can DA act? The sphere of influence of released DA depends on local diffusion and uptake characteristics, which influence absolute [DA]o at a given time after release (Stamford et al., 1988; Garris et al., 1994; Gonon et al., 2000; Cragg et al., 2001; Venton et al., 2”