Dopamine depresses excitatory synaptic transmission onto rat subicular neurons via presynaptic D1-like dopamine receptors

Item Type:	Article
Title:	Dopamine depresses excitatory synaptic transmission onto rat subicular neurons via presynaptic D1-like dopamine receptors
Creators Name:	Behr, J. and Gloveli, T. and Schmitz, D. and Heinemann, U.
Abstract:	Schizophrenia is considered to be associated with an abnormal functioning of the hippocampal output. The high clinical potency of antipsychotics that act as antagonists at dopamine (DA) receptors indicate a hyperfunction of the dopaminergic system. The subiculum obtains information from area CA1 and the entorhinal cortex and represents the major output region of the hippocampal complex. To clarify whether an enhanced dopaminergic activity alters the hippocampal output, the effect of DA on alveus- and perforant path-evoked excitatory postsynaptic currents (EPSCs) in subicular neurons was examined using conventional intracellular and whole cell voltage-clamp recordings. Dopamine (100 microM) depressed alveus-elicited (S)-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSCs to 56 +/- 8% of control while perforant path-evoked EPSCs were attenuated to only 76 +/- 7% of control. Dopamine had no effect on the EPSC kinetics. Dopamine reduced the frequency of spontaneous miniature EPSCs without affecting their amplitudes. The sensitivity of subicular neurons to the glutamate receptor agonist (S)-{alpha}-amino-3-hydoxy-5-methyl-4-isoxazolepropionic acid was unchanged by DA pretreatment, excluding a postsynaptic mechanism for the observed reduction of excitatory synaptic transmission. The effect of DA on evoked EPSCs was mimicked by the D1 receptor agonist SFK 38393 and partially antagonized by the D1 receptor antagonist SCH 23390. While the D2 receptor agonist quinelorane failed to reduce the EPSCs, the D2 receptor antagonist sulpiride did not block the action of DA. The results indicate that DA strongly depresses the hippocampal and the entorhinal excitatory input onto subicular neurons by decreasing the glutamate release following activation of presynaptic D1-like DA receptors.
Keywords:	{alpha}-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid, 2,3,4,5-Tetrahydro-7,8-Dihydroxy-1-Phenyl-1H-3-Benzazepine, Benzazepines, Dopamine, Dopamine Agonists, Dopamine Antagonists, Dopamine D1 Receptors, Entorhinal Cortex, Excitatory Amino Acid Agonists, Excitatory Postsynaptic Potentials, Glutamic Acid, Hippocampus, Neurons, Patch-Clamp Techniques, Perforant Pathway, Presynaptic Terminals, Quinolines, Sulpiride, Synaptic Transmission, Animals, Rats
Source:	Journal of Neurophysiology
ISSN:	0022-3077
Publisher:	American Physiological Society
Volume:	84
Number:	1
Page Range:	112-119
Date:	July 2000
Official Publication:	http://jn.physiology.org/content/84/1/112.long
PubMed:	View item in PubMed

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