Phasic Dopamine Release Drives Rapid Activation of Striatal D2-receptors

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2014 Sep 23

PMID 25242218

Citations 74

Authors

Pamela F Marcott

Aphroditi A Mamaligas

Christopher P Ford

Affiliations

Soon will be listed here.

Abstract

Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum, and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory postsynaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals.

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References

Schultz W . Behavioral dopamine signals. Trends Neurosci. 2007; 30(5):203-10. DOI: 10.1016/j.tins.2007.03.007. View

Schmitz Y, Benoit-Marand M, Gonon F, Sulzer D . Presynaptic regulation of dopaminergic neurotransmission. J Neurochem. 2003; 87(2):273-89. DOI: 10.1046/j.1471-4159.2003.02050.x. View

Grace A, Floresco S, Goto Y, Lodge D . Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci. 2007; 30(5):220-7. DOI: 10.1016/j.tins.2007.03.003. View

Lovinger D . Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum. Neuropharmacology. 2010; 58(7):951-61. PMC: 2849868. DOI: 10.1016/j.neuropharm.2010.01.008. View

Kenakin T . The classification of seven transmembrane receptors in recombinant expression systems. Pharmacol Rev. 1996; 48(3):413-63. View

Graybiel A . Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci. 1990; 13(7):244-54. DOI: 10.1016/0166-2236(90)90104-i. View

Chen R, Tilley M, Wei H, Zhou F, Zhou F, Ching S . Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter. Proc Natl Acad Sci U S A. 2006; 103(24):9333-8. PMC: 1482610. DOI: 10.1073/pnas.0600905103. View

Karschin C, DISSMANN E, Stuhmer W, Karschin A . IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J Neurosci. 1996; 16(11):3559-70. PMC: 6578832. View

Richfield E, Penney J, Young A . Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system. Neuroscience. 1989; 30(3):767-77. DOI: 10.1016/0306-4522(89)90168-1. View

10.

Bromberg-Martin E, Hikosaka O . Midbrain dopamine neurons signal preference for advance information about upcoming rewards. Neuron. 2009; 63(1):119-26. PMC: 2723053. DOI: 10.1016/j.neuron.2009.06.009. View

11.

Berke J, Hyman S . Addiction, dopamine, and the molecular mechanisms of memory. Neuron. 2000; 25(3):515-32. DOI: 10.1016/s0896-6273(00)81056-9. View

12.

Albin R, Young A, Penney J . The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989; 12(10):366-75. DOI: 10.1016/0166-2236(89)90074-x. View

13.

Chergui K, Suaud-Chagny M, Gonon F . Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo. Neuroscience. 1994; 62(3):641-5. DOI: 10.1016/0306-4522(94)90465-0. View

14.

Keefe K, Zigmond M, Abercrombie E . In vivo regulation of extracellular dopamine in the neostriatum: influence of impulse activity and local excitatory amino acids. J Neural Transm Gen Sect. 1993; 91(2-3):223-40. DOI: 10.1007/BF01245233. View

15.

Kenakin T . New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2. Br J Pharmacol. 2012; 168(3):554-75. PMC: 3579279. DOI: 10.1111/j.1476-5381.2012.02223.x. View

16.

Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M . Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem. 1995; 270(48):28660-7. DOI: 10.1074/jbc.270.48.28660. View

17.

Kravitz A, Freeze B, Parker P, Kay K, Thwin M, Deisseroth K . Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466(7306):622-6. PMC: 3552484. DOI: 10.1038/nature09159. View

18.

Liao Y, Jan Y, Jan L . Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. J Neurosci. 1996; 16(22):7137-50. PMC: 6578936. View

19.

Ostrom R, Post S, Insel P . Stoichiometry and compartmentation in G protein-coupled receptor signaling: implications for therapeutic interventions involving G(s). J Pharmacol Exp Ther. 2000; 294(2):407-12. View

20.

Gerfen C, Surmeier D . Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011; 34:441-66. PMC: 3487690. DOI: 10.1146/annurev-neuro-061010-113641. View