Dopamine Presynaptically and Heterogeneously Modulates Nucleus Accumbens Medium-spiny Neuron GABA Synapses in Vitro

Overview

Journal BMC Neurosci

Publisher Biomed Central

Specialty Neurology

Date 2006 Jul 4

PMID 16813648

Citations 14

Authors

Daron Geldwert

J Madison Norris

Igor G Feldman

Joshua J Schulman

Myra P Joyce

Stephen Rayport

Affiliations

Soon will be listed here.

Abstract

Background: The striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make autaptic connections that provide access to single, identified medium-spiny to medium-spiny neuron synaptic connections.

Results: We examined medium-spiny neuron autaptic connections in postnatal cultures from the nucleus accumbens, the ventral part of the striatal complex. These connections were subject to presynaptic dopamine modulation. D1-like receptors mediated either inhibition or facilitation, while D2-like receptors predominantly mediated inhibition. Many connections showed both D1 and D2 modulation, consistent with a significant functional colocalization of D1 and D2-like receptors at presynaptic sites. These same connections were subject to GABAA, GABAB, norepinephrine and serotonin modulation, revealing a multiplicity of modulatory autoreceptors and heteroreceptors on individual varicosities. In some instances, autaptic connections had two components that were differentially modulated by dopamine agonists, suggesting that dopamine receptors could be distributed heterogeneously on the presynaptic varicosities making up a single synaptic (i.e. autaptic) connection.

Conclusion: Differential trafficking of dopamine receptors to different presynaptic varicosities could explain the many controversial studies reporting widely varying degrees of dopamine receptor colocalization in medium-spiny neurons, as well as more generally the diversity of dopamine actions in target areas. Longer-term changes in the modulatory actions of dopamine in the striatal complex could be due to plasticity in the presynaptic distribution of dopamine receptors on medium-spiny neuron varicosities.

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References

Shetreat M, Lin L, Wong A, Rayport S . Visualization of D1 dopamine receptors on living nucleus accumbens neurons and their colocalization with D2 receptors. J Neurochem. 1996; 66(4):1475-82. DOI: 10.1046/j.1471-4159.1996.66041475.x. View

Betz W, Mao F, Smith C . Imaging exocytosis and endocytosis. Curr Opin Neurobiol. 1996; 6(3):365-71. DOI: 10.1016/s0959-4388(96)80121-8. View

Surmeier D, Song W, Yan Z . Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci. 1996; 16(20):6579-91. PMC: 6578920. View

Isaacson J, Hille B . GABA(B)-mediated presynaptic inhibition of excitatory transmission and synaptic vesicle dynamics in cultured hippocampal neurons. Neuron. 1997; 18(1):143-52. DOI: 10.1016/s0896-6273(01)80053-2. View

Pickel V, Nirenberg M, Milner T . Ultrastructural view of central catecholaminergic transmission: immunocytochemical localization of synthesizing enzymes, transporters and receptors. J Neurocytol. 1996; 25(12):843-56. DOI: 10.1007/BF02284846. View

Delle Donne K, Sesack S, Pickel V . Ultrastructural immunocytochemical localization of the dopamine D2 receptor within GABAergic neurons of the rat striatum. Brain Res. 1997; 746(1-2):239-55. DOI: 10.1016/s0006-8993(96)01226-7. View

Ueno S, Bracamontes J, Zorumski C, Weiss D, Steinbach J . Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor. J Neurosci. 1997; 17(2):625-34. PMC: 6573228. View

Radnikow G, Misgeld U . Dopamine D1 receptors facilitate GABAA synaptic currents in the rat substantia nigra pars reticulata. J Neurosci. 1998; 18(6):2009-16. PMC: 6792937. View

Auger C, Kondo S, Marty A . Multivesicular release at single functional synaptic sites in cerebellar stellate and basket cells. J Neurosci. 1998; 18(12):4532-47. PMC: 6792676. View

10.

Wiens B, Nelson C, Neve K . Contribution of serine residues to constitutive and agonist-induced signaling via the D2S dopamine receptor: evidence for multiple, agonist-specific active conformations. Mol Pharmacol. 1998; 54(2):435-44. DOI: 10.1124/mol.54.2.435. View

11.

Delgado A, Sierra A, Querejeta E, Valdiosera R, Aceves J . Inhibitory control of the GABAergic transmission in the rat neostriatum by D2 dopamine receptors. Neuroscience. 2000; 95(4):1043-8. DOI: 10.1016/s0306-4522(99)00495-9. View

12.

Aizman O, Brismar H, Uhlen P, Zettergren E, Levey A, Forssberg H . Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons. Nat Neurosci. 2000; 3(3):226-30. DOI: 10.1038/72929. View

13.

Yung K, Bolam J . Localization of dopamine D1 and D2 receptors in the rat neostriatum: synaptic interaction with glutamate- and GABA-containing axonal terminals. Synapse. 2000; 38(4):413-20. DOI: 10.1002/1098-2396(20001215)38:4<413::AID-SYN6>3.0.CO;2-V. View

14.

Parent A, Sato F, Wu Y, Gauthier J, Levesque M, Parent M . Organization of the basal ganglia: the importance of axonal collateralization. Trends Neurosci. 2000; 23(10 Suppl):S20-7. DOI: 10.1016/s1471-1931(00)00022-7. View

15.

Cooper A, Stanford I . Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABA(A) IPSCs in vitro. Neuropharmacology. 2001; 41(1):62-71. DOI: 10.1016/s0028-3908(01)00038-7. View

16.

Benoit-Marand M, Borrelli E, Gonon F . Inhibition of dopamine release via presynaptic D2 receptors: time course and functional characteristics in vivo. J Neurosci. 2001; 21(23):9134-41. PMC: 6763925. View

17.

Wang H, Pickel V . Dopamine D2 receptors are present in prefrontal cortical afferents and their targets in patches of the rat caudate-putamen nucleus. J Comp Neurol. 2002; 442(4):392-404. DOI: 10.1002/cne.10086. View

18.

Mengual E, Pickel V . Ultrastructural immunocytochemical localization of the dopamine D2 receptor and tyrosine hydroxylase in the rat ventral pallidum. Synapse. 2002; 43(3):151-62. DOI: 10.1002/syn.10033. View

19.

Yasumoto S, Tanaka E, Hattori G, Maeda H, Higashi H . Direct and indirect actions of dopamine on the membrane potential in medium spiny neurons of the mouse neostriatum. J Neurophysiol. 2002; 87(3):1234-43. DOI: 10.1152/jn.00514.2001. View

20.

Tunstall M, Oorschot D, Kean A, Wickens J . Inhibitory interactions between spiny projection neurons in the rat striatum. J Neurophysiol. 2002; 88(3):1263-9. DOI: 10.1152/jn.2002.88.3.1263. View