| Description: |
Dendritic release of dopamine in the ventral tegmental area acts on D2-dopamine receptors to mediate an inhibitory postsynaptic current (IPSC). This study examines how the rise and fall in extracellular dopamine regulates the kinetics of the IPSC. Extracellular dopamine was measured electrochemically during simultaneous recording of the IPSC. Both the rise and fall of dopamine were rapid relative to the IPSC, suggesting that G-protein dependent potassium channel activation determined the time course of the IPSC. The kinetics of D2 receptor dependent activation of potassium currents was studied using outside-out patch recordings and rapid application of dopamine. Dopamine applied at a minimum concentration of 10 µM for a maximum of 100 ms mimicked the IPSC. Shorter applications of higher concentrations did not change the kinetics of the outward current. These measurements were used to construct a model predicting that dopamine travels less then 500 nm from the site of release before binding to D2 receptors.
Selected Publications:
Dang, V.C. and Williams, J.T. (2004)
Chronic morphine treatment reduces recovery from opioid desensitization. J. Neurosci. 24:7699-7706.
Beckstead, M.J., Grandy, D.K., Wickman, K., and Williams, J.T. (2004)
Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron 42:939-946.
Dumont, E.C. and Williams, J.T. (2004)
Noradrenaline triggers GABAA-inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area. J. Neurosci. 24:8198-8204.
Paladini, C.A., Mitchell, J.M., Williams, J.T., and Mark, G.P. (2004)
Cocaine self-administration selectively decreases noradrenergic regulation of metabotropic glutamate receptor-mediated inhibition in dopamine neurons.
J. Neurosci. 24:5209-5215.
Paladini, C.A. and Williams, J.T. (2004)
Noradrenergic inhibition of midbrain dopamine neurons. J. Neurosci. 24:4568-4575.
Paladini, C.A., Robinson, S., Morikawa, H., Williams, J.T., and Palmiter, R. (2003) Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism.
Proc. Natl. Acad. Sci. USA 100:2866-2871.
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