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The Journal of Neuroscience, September 3, 2008, 28(36):8908-8913; doi:10.1523/JNEUROSCI.1526-08.2008

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Brief Communications
Midbrain Dopamine Neurons: Projection Target Determines Action Potential Duration and Dopamine D₂ Receptor Inhibition

Elyssa B. Margolis,¹ Jennifer M. Mitchell,¹ Junko Ishikawa,¹ Gregory O. Hjelmstad,^1,2 and Howard L. Fields^1,2

¹Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, and ²Department of Neurology and Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, California 94143-0114

Correspondence should be addressed to Elyssa B. Margolis, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA 94608. Email: elyssam{at}gallo.ucsf.edu

Broad action potentials (APs) and dopamine (DA) D₂ receptor (D₂R)-mediated inhibition are widely used to identify midbrain DA neurons. However, when these measures are taken alone they do not predict DA content in ventral tegmental area (VTA) neurons. In fact, some VTA neuronal properties correlate better with projection target than neurotransmitter content. Here we report that amygdala (AMYG)-projecting VTA DA neurons have brief APs and lack D₂R agonist (quinpirole; 1 µM) autoinhibition. However, they are hyperpolarized by both the GABA_B agonist baclofen (1 µM) and the -opioid receptor agonist U69593 [GenBank] [(+)-(5,7,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide; 1 µM]. Furthermore, we show that accurate prediction of DA content in VTA neurons is possible when the projection target is known: in both nucleus accumbens- and AMYG-projecting neural populations, AP durations are significantly longer in DA than non-DA neurons. Among prefrontal cortex-projecting neurons, quinpirole sensitivity, but not AP duration, is a predictor of DA content. Therefore, in the VTA, AP duration and inhibition by D₂R agonists may be valid markers of DA content in neurons of known projection target.

Key words: dopamine; ventral tegmental area; nucleus accumbens; amygdala; D₂ receptor; -opioid

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Received April 8, 2008; revised July 25, 2008; accepted Aug. 4, 2008.

Correspondence should be addressed to Elyssa B. Margolis, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA 94608. Email: elyssam{at}gallo.ucsf.edu

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