Biomaterial Database

Dopaminergic modulation of excitatory postsynaptic currents in rat neostriatal neurons. 1997

M Umemiya, and L A Raymond

Department of Psychiatry, University of British Columbia, Vancouver, Canada.

Gamma-aminobutyric acid (GABA)-containing medium spiny neurons constitute approximately 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 microM 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 D1-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 microM, SKF 38393 resulted in a 29 +/- 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D1-selective antagonist, SCH 23390 (10 microM). On the other hand, 5 microM 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 D1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement.

UI	MeSH Term	Description	Entries
D007608	Kainic Acid	(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.	Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017072	Neostriatum	The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018091	Receptors, AMPA	A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).	AMPA Receptors,Quisqualate Receptors,AMPA Receptor,Quisqualate Receptor,Receptor, AMPA,Receptor, Quisqualate,Receptors, Quisqualate