Dopamine inhibits GABA transmission from the globus pallidus to the thalamic reticular nucleus via presynaptic D4 receptors

• Published in: Neuroscience Vol. 169; no. 4; pp. 1672 - 1681
• Main Authors: Gasca-Martinez, D, Hernandez, A, Sierra, A, Valdiosera, R, Anaya-Martinez, V, Floran, B, Erlij, D, Aceves, J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.09.2010; Elsevier
• Subjects: Animals; basal ganglia; Biological and medical sciences; D4-agonists; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - pharmacology; Dopamine - physiology; dopamine receptors; Fundamental and applied biological sciences. Psychology; gamma-Aminobutyric Acid - physiology; Globus Pallidus - cytology; Globus Pallidus - drug effects; Globus Pallidus - metabolism; Intralaminar Thalamic Nuclei - drug effects; Intralaminar Thalamic Nuclei - metabolism; Male; Medical sciences; Neural Pathways - cytology; Neural Pathways - drug effects; Neural Pathways - metabolism; Neurology; Organ Culture Techniques; Parkinson's disease; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Wistar; Receptors, Dopamine D4 - agonists; Receptors, Dopamine D4 - physiology; sleep disorders; Sleep. Vigilance; thalamus; Vertebrates: nervous system and sense organs; ABC; basal ganglia; Parkinson's disease; excessive daytime sleepiness; PD 168,077; low threshold-activation Ca 2+ current; rapid eye movement; l-745; EDS; miniature inhibitory postsynaptic currents; Thal; ic; l-745,870; 3,3′-diaminobenzidine tetrahydrochloride; globus pallidus; thalamus; sleep disorders; V m; inhibitory postsynaptic currents; D4-agonists; DAB; mIPSCs; CPu; GP; avidin–biotin–peroxidase complex; caudate–putamen; ACSF; artificial cerebrospinal fluid; TRn; dopamine receptors; PD; IPSCs; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; membrane potential; thalamic reticular nucleus; MPTP; REM; I T; internal capsule; IT; Vm; Agonist; Central nervous system; Parkinson disease; Reticular nucleus; Pallidum; Encephalon; Thalamus; Degenerative disease; D4 Dopamine receptor; Nervous system diseases; Dopamine; Dopamine receptor; Basal ganglion; Catecholamine; Cerebral disorder; Sleep; Central nervous system disease; Neurotransmitter; GABA; Extrapyramidal syndrome
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.05.048

Abstract The globus pallidus sends a significant GABAergic projection to the thalamic reticular nucleus. Because pallidal neurons express D4-dopamine receptors, we have explored their presence on pallidoreticular terminals by studying the effect of dopamine and D4-receptor agonists on the GABAergic transmission in the thalamic reticular nucleus. We made whole-cell recordings of inhibitory postsynaptic currents (IPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in the thalamic reticular neurons. Dopamine consistently reduced the IPSCs. The effect of dopamine was associated with paired-pulse facilitation, indicating a presynaptic location of the receptors. The effect of dopamine was also measured on the mIPSCs, reducing their frequency but not affecting their amplitude, which also suggests a presynaptic site of action. The selective D4-receptor agonist PD 168,077 also reduced the IPSCs, which was also associated with paired-pulse facilitation. In addition, this agonist reduced the frequency of the mIPSCs with no effect on their amplitude. The D4-receptor antagonist l -745,870 totally blocked the effect of the D4-receptor agonist, indicating the specificity of its effect. To verify the location of the receptors on the pallidal terminals, these were eliminated by injecting kainic acid into the globus pallidus. Kainic acid produced a drastic (80%) fall in the globus pallidus neuronal population. In this condition, the effect of the activation of D4 receptors both on the IPSCs and mIPSCs was prevented, thus indicating that the location of the receptors was on the pallidal terminals. Our results demonstrate that dopamine controls the activity of the thalamic reticular neurons by regulating the inhibitory input from the globus pallidus.