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Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons

Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons Abstract Umemiya, Masashi and Lynn A. Raymond. Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. J. Neurophysiol. 78: 1248–1255, 1997. γ-aminobutyric acid (GABA)-containing medium spiny neurons constitute ∼90% of the neuronal population in the neostriatum (caudate and putamen) and play an important role in motor programming. Cortical glutamatergic afferents provide the main excitatory drive for these neurons, whereas nigral dopaminergic neurons play a crucial role in regulating their activity. To further investigate the mechanisms underlying the dopaminergic modulation of medium spiny neuronal activity, we tested the effect of dopamine receptor agonists on excitatory synaptic transmission recorded from these neurons. Excitatory postsynaptic currents (EPSCs) were evoked by local stimulation and recorded from medium spiny neurons in postnatal rat striatal thin brain slices. Recordings were made using the whole cell patch-clamp technique under voltage clamp and conditions that selected for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 μM dopamine resulted in a 33 ± 11% (mean ± SE) decrease in the amplitude of evoked EPSCs, an effect that developed during seconds. The relative variability in amplitude of dopamine's effects on medium spiny neuron EPSCs may reflect activation of different receptor subtypes with opposing effects. In contrast to the results with dopamine, incubation of slices in SKF 38393, a D 1 -type dopamine receptor selective agonist, resulted in dose-dependent potentiation of the medium spiny neuron EPSC that developed during several minutes. At a concentration of 5 μM, SKF 38393 resulted in a 29 ± 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D 1 -selective antagonist, SCH 23390 (10 μM). On the other hand, 5 μM SKF 38393 had no apparent effect on medium spiny neuron currents activated by exogenous application of glutamate or kainate. However, because of the inherent limitations of rapid agonist perfusion in the brain slice preparation (caused by slow agonist diffusion and rapid glutamate receptor desensitization) and because of anatomic evidence that colocalizes D 1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D 1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D 1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D 1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement. Footnotes Address for reprint requests: L. A. Raymond, Division of Neurological Sciences, Dept. of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Present address of M. Umemiya: Dept. of Neurophysiology, Tohoku University School of Medicine, Sendhai 980-77, Japan. Copyright © 1997 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurophysiology The American Physiological Society

Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons

Umemiya, Masashi; Raymond, Lynn A.
Journal of Neurophysiology , Volume 78 (3): 1248 – Sep 1, 1997
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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0022-3077
eISSN
1522-1598
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Abstract

Abstract Umemiya, Masashi and Lynn A. Raymond. Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. J. Neurophysiol. 78: 1248–1255, 1997. γ-aminobutyric acid (GABA)-containing medium spiny neurons constitute ∼90% of the neuronal population in the neostriatum (caudate and putamen) and play an important role in motor programming. Cortical glutamatergic afferents provide the main excitatory drive for these neurons, whereas nigral dopaminergic neurons play a crucial role in regulating their activity. To further investigate the mechanisms underlying the dopaminergic modulation of medium spiny neuronal activity, we tested the effect of dopamine receptor agonists on excitatory synaptic transmission recorded from these neurons. Excitatory postsynaptic currents (EPSCs) were evoked by local stimulation and recorded from medium spiny neurons in postnatal rat striatal thin brain slices. Recordings were made using the whole cell patch-clamp technique under voltage clamp and conditions that selected for the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 μM dopamine resulted in a 33 ± 11% (mean ± SE) decrease in the amplitude of evoked EPSCs, an effect that developed during seconds. The relative variability in amplitude of dopamine's effects on medium spiny neuron EPSCs may reflect activation of different receptor subtypes with opposing effects. In contrast to the results with dopamine, incubation of slices in SKF 38393, a D 1 -type dopamine receptor selective agonist, resulted in dose-dependent potentiation of the medium spiny neuron EPSC that developed during several minutes. At a concentration of 5 μM, SKF 38393 resulted in a 29 ± 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D 1 -selective antagonist, SCH 23390 (10 μM). On the other hand, 5 μM SKF 38393 had no apparent effect on medium spiny neuron currents activated by exogenous application of glutamate or kainate. However, because of the inherent limitations of rapid agonist perfusion in the brain slice preparation (caused by slow agonist diffusion and rapid glutamate receptor desensitization) and because of anatomic evidence that colocalizes D 1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D 1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D 1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D 1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement. Footnotes Address for reprint requests: L. A. Raymond, Division of Neurological Sciences, Dept. of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada. Present address of M. Umemiya: Dept. of Neurophysiology, Tohoku University School of Medicine, Sendhai 980-77, Japan. Copyright © 1997 the American Physiological Society

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Journal of Neurophysiology – The American Physiological Society

Published: Sep 1, 1997

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