Abstract
Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit somatodendritic release of DA. Previous studies indicate a difference between the Ca2+ dependence of somatodendritic DA release in the SNc and that of axonal DA release in dorsal striatum. Here, we evaluated the Ca2+ dependence of DA release in the VTA and nucleus accumbens (NAc) shell for comparison with that in the SNc and dorsal striatum. Release of DA was elicited by single-pulse stimulation in guinea-pig brain slices and monitored with subsecond resolution using carbon-fiber microelectrodes and fast-scan cyclic voltammetry. In dorsal striatum and NAc, DA release was not detectable at extracellular Ca2+ concentrations ([Ca2+]o) below 1 mM; however, a progressive increase in evoked extracellular DA concentration ([DA]o) was seen with [Ca2+]o ≥ 1.5 mM. By contrast, in SNc and VTA, robust increases in [DA]o could be elicited in 0.25 mM [Ca2+]o that were ∼60% of those seen in 1.5 mM [Ca2+]o. In SNc, a plateau in single-pulse evoked [DA]o was seen at [Ca2+]o ≥ 1.5 mM, mirroring the release plateau reported previously for pulse-train stimulation in SNc. In VTA, however, evoked [DA]o increased progressively throughout the range of [Ca2+]o tested (up to 3.0 mM). These functional data are consistent with the microanatomy of the VTA, which includes DA axon collaterals as well as DA somata and dendrites. Differences between axonal and somatodendritic release data were quantified using Hill analysis, which showed that the Ca2+ dependence of axonal DA release is low affinity with high Ca2+ cooperativity, whereas somatodendritic release is high affinity with low cooperativity. Moreover, this analysis revealed the dual nature of DA release in the VTA, with both somatodendritic and axonal contributions.
Highlights
Brain dopamine (DA) arises primarily from two midbrain cell groups, the substantia nigra pars compacta (SNc; A9) and the ventral tegmental area (VTA; A10; Dahlström and Fuxe, 1964), both of which project ipsilaterally via the median forebrain bundle to forebrain regions (Ungerstedt, 1971; Fallon and Moore, 1978)
That study had two limitations, : first, the low Ca2+ levels tested were undefined; second, DA release was evoked by pulse-train stimulation, which elicits the concurrent release of glutamate and GABA that can modulate DA release in both the dorsal striatum and SNc (Chen and Rice, 2002; Avshalumov et al, 2003; Patel et al, 2009)
Ca2+ dependence of single-pulse evoked DA release in dorsal striatum and SNc In dorsal striatum, axonal DA release elicited by a single-pulse showed a marked dependence on [Ca2+]o (Figures 1A,B)
Summary
Brain dopamine (DA) arises primarily from two midbrain cell groups, the substantia nigra pars compacta (SNc; A9) and the ventral tegmental area (VTA; A10; Dahlström and Fuxe, 1964), both of which project ipsilaterally via the median forebrain bundle to forebrain regions (Ungerstedt, 1971; Fallon and Moore, 1978). Release of DA occurs in both SNc and VTA (Björkland and Lindvall, 1975; Geffen et al, 1976; Nieoullon et al, 1977; Rice et al, 1994, 1997; Iravani et al, 1996; Jaffe et al, 1998; Chen and Rice, 2001, 2002; Patel et al, 2009). Previous comparison of somatodendritic DA release in the SNc vs axonal DA release in dorsal striatum revealed a strikingly lower Ca2+ dependence of somatodendritic DA release (Chen and Rice, 2001). The Ca2+ dependence of DA release in NAc or VTA was not examined in that study
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.