Dopamine profoundly suppresses excitatory transmission in neonatal rat hippocampus via phosphatidylinositol-linked D1-like receptor

Abstract

Dopamine modulates synaptic transmission in various brain regions. The disorder of dopamine system may be related to neurodevelopmental dysfunction. However, the action of dopamine on synaptic transmission during development is largely unknown. We studied the effect of dopamine on GABAergic and glutamatergic transmission in neonatal rat hippocampus from the early period of synapse formation by whole-cell patch-clamp recordings from CA1 pyramidal cells. Dopamine (100 μM) profoundly decreased the amplitude of GABA A receptor-mediated postsynaptic currents (GABA A-PSCs) to 32.2±5.4% (mean±S.E.M., EC 50: 2.9 μM) in the first postnatal week, when GABA provides excitatory drive. Dopamine also decreased the amplitude of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) to 29.1±2.7% (EC 50: 18.7 μM) in the second postnatal week, when glutamate responses first appear. The dopamine-induced inhibition declined after these periods and became only partial after postnatal day 30. Further we identified the receptor subtype involved in the dopamine-induced inhibition as phosphatidylinositol-linked D1-like receptor, since 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol hydrobromide (SKF 83959), a selective agonist for phosphatidylinositol-linked D1-like receptor, clearly mimicked the action of dopamine, and 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phospholipase C, significantly reduced the dopamine-induced inhibition. Dopamine did not change the response to puff-applied GABA or kainic acid, nor the amplitude of miniature GABA A-PSCs or miniature EPSCs. These results suggest that the activation of phosphatidylinositol-linked D1-like receptor profoundly suppresses the excitatory transmission during the early period of synapse formation in the developing hippocampus by presynaptic mechanisms. This study firstly demonstrates the effect of phosphatidylinositol-linked D1-like receptor on synaptic transmission.