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The Journal of Neuroscience, July 15, 1998, 18(14):5180-5190

Dopamine D₁-Like Receptor Activation Excites Rat Striatal Large Aspiny Neurons In Vitro

Toshihiko Aosaki¹, Kazutoshi Kiuchi², and Yasuo Kawaguchi¹

¹ Laboratory for Neural Circuits and ² Laboratory for Genes of Motor Systems, Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research (RIKEN), Nagoya, Aichi 463-0003, Japan

The aim of this study was to elucidate electrophysiologically the actions of dopamine and SKF38393, a D₁-like dopamine receptor agonist, on the membrane excitability of striatal large aspiny neurons (cholinergic interneurons). Whole-cell and perforated patch-clamp recordings were made of striatal cholinergic neurons in rat brain slice preparations. Bath application of dopamine (1-100 µM) evoked a depolarization/inward current with an increase, a decrease, or no change in membrane conductance in a dose-dependent manner. This effect was antagonized by SCH23390, a D₁-like dopamine receptor antagonist. The current-voltage relationships of the dopamine-induced current determined in 23 cells suggested two conductances. In 10 cells the current reversed at 94 mV, approximately equal to the K⁺ equilibrium potential (E_K); in three cells the I-V curves remained parallel, whereas in 10 cells the current reversed at 42 mV, which suggested an involvement of a cation permeable channel. Change in external K⁺ concentration shifted the reversal potential as expected for E_k in low Na⁺ solution. The current observed in 2 mM Ba²⁺-containing solution reversed at 28 mV. These actions of dopamine were mimicked by application of SKF38393 (1-50 µM) or forskolin (10 µM), an adenylyl cyclase activator, and were blocked by SCH23390 (10 µM) or SQ22536 (300 µM), an inhibitor of adenylyl cyclase. These data indicate, first, that dopamine depolarizes the striatal large aspiny neurons by a D₁-mediated suppression of resting K⁺ conductance and an opening of a nonselective cation channel and, second, that both mechanisms are mediated by an adenylyl cyclase-dependent pathway.

Key words: dopamine; acetylcholine; striatum; basal ganglia; cholinergic neurons; giant aspiny neurons; patch clamp; slice; electrophysiology

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18145180-11$05.00/0

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