Opposite Influences of Endogenous Dopamine D1and D2Receptor Activation on Activity States and Electrophysiological Properties of Striatal Neurons: Studies CombiningIn VivoIntracellular Recordings and Reverse Microdialysis

Abstract

The tonic influence of dopamine D1 and D2 receptors on the activity of striatal neurons in vivo was investigated by performing intracellular recordings concurrently with reverse microdialysis in chloral hydrate-anesthetized rats. Striatal neurons were recorded in the vicinity of the microdialysis probe to assess their activity during infusions of artificial CSF (aCSF), the D1 receptor antagonist SCH 23390 (10 microm), or the D2 receptor antagonist eticlopride (20 microm). SCH 23390 perfusion decreased the excitability of striatal neurons exhibiting electrophysiological characteristics of spiny projection cells as evidenced by a decrease in the maximal depolarized membrane potential, a decrease in the amplitude of up-state events, and an increase in the intracellular current injection amplitude required to elicit an action potential. Conversely, a marked depolarization of up- and down-state membrane potential modes, a decrease in the amplitude of intracellular current injection required to elicit an action potential, and an increase in the number of spikes evoked by depolarizing current steps were observed in striatal neurons after local eticlopride infusion. A significant increase in maximal EPSP amplitude evoked by electrical stimulation of the prefrontal cortex was also observed during local eticlopride but not SCH 23390 infusion. These results indicate that in intact systems, ongoing dopaminergic neurotransmission exerts a powerful tonic modulatory influence on the up- and down-state membrane properties of striatal neurons and controls their excitability differentially via both D1- and D2-like receptors. Moreover, a significant component of D2 receptor-mediated inhibition of striatal neuron activity in vivo occurs via suppression of excitatory synaptic transmission.