Dopaminergic enhancement of excitatory synaptic transmission in layer II entorhinal neurons is dependent on D₁-like receptor-mediated signaling.
The modulatory neurotransmitter dopamine induces concentration-dependent changes in synaptic transmission in the entorhinal cortex, in which high concentrations of dopamine suppress evoked excitatory postsynaptic potentials (EPSPs) and lower concentrations induce an acute synaptic facilitation. Whole-cell current-clamp recordings were used to investigate the dopaminergic facilitation of synaptic responses in layer II neurons of the rat lateral entorhinal cortex. A constant bath application of 1 μM dopamine resulted in a consistent facilitation of EPSPs evoked in layer II fan cells by layer I stimulation; the size of the facilitation was more variable in pyramidal neurons, and synaptic responses in a small group of multiform neurons were not modulated by dopamine. Isolated inhibitory synaptic responses were not affected by dopamine, and the facilitation of EPSPs was not associated with a change in paired-pulse facilitation ratio. Voltage-clamp recordings of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor-mediated excitatory postsynaptic currents (EPSCs) were facilitated by dopamine, but N-methyl-D-aspartate receptor-mediated currents were not. Bath application of the dopamine D₁-like receptor blocker SCH23390 (50 μM), but not the D₂-like receptor blocker sulpiride (50 μM), prevented the facilitation, indicating that it is dependent upon D₁-like receptor activation. Dopamine D₁ receptors lead to activation of protein kinase A (PKA), and including the PKA inhibitor H-89 or KT 5720 in the recording pipette solution prevented the facilitation of EPSCs. PKA-dependent phosphorylation of inhibitor 1 or the dopamine- and cAMP-regulated protein phosphatase (DARPP-32) can lead to a facilitation of AMPA receptor responses by inhibiting the activity of protein phosphatase 1 (PP1) that reduces dephosphorylation of AMPA receptors, and we found here that inhibition of PP1 occluded the facilitatory effect of dopamine. The dopamine-induced facilitation of AMPA receptor-mediated synaptic responses in layer II neurons of the lateral entorhinal cortex is therefore likely mediated via a D₁ receptor-dependent increase in PKA activity and a resulting inhibition in PP1-dependent dephosphorylation of AMPA receptors.
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada.
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Glovaci
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada.
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Caruana
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada. Electronic address: andrew.chapman@concordia.ca.
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Chapman
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases; D054645:Protein Phosphatase 1; D004298:Dopamine
(2R)-amino-5-phosphonopentanoate; 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid; 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile; ACSF; AMPA; APV; CNQX; DARPP-32; EGTA; EPSC; EPSP; HEPES; N-methyl-d-aspartate; NMDA; PKA; PP1; PP2A; artificial cerebrospinal fluid; dopamine; dopamine- and cyclic AMP-regulated phosphoprotein; entorhinal cortex; ethylene glycol tetraacetic acid; excitatory postsynaptic current; excitatory postsynaptic potential; protein kinase A; protein phosphatase 1; protein phosphatase 2A; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid