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Volume 17, Number 9, Issue of May 1, 1997 pp. 3334-3342
Copyright ©1997 Society for Neuroscience

D₁ Receptor Activation Enhances Evoked Discharge in Neostriatal Medium Spiny Neurons by Modulating an L-Type Ca²⁺ Conductance

Received Nov. 12, 1996; revised Feb. 18, 1997; accepted Feb. 19, 1996.

Salvador Hernández-López¹, José Bargas¹, D. James Surmeier², Arturo Reyes¹, and Elvira Galarraga¹

¹ Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autonoma de Mexico, México City DF, 04510 México, and ² Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, Tennessee 38163

Most in vitro studies of D₁ dopaminergic modulation of excitability in neostriatal medium spiny neurons have revealed inhibitory effects. Yet studies made in more intact preparations have shown that D₁ receptors can enhance or inhibit the responses to excitatory stimuli. One explanation for these differences is that the effects of D₁ receptors on excitability are dependent on changes in the membrane potential occurring in response to cortical inputs that are seen only in intact preparations. To test this hypothesis, we obtained voltage recordings from medium spiny neurons in slices and examined the impact of D₁ receptor stimulation at depolarized and hyperpolarized membrane potentials. As previously reported, evoked discharge was inhibited by D₁ agonists when holding at negative membrane potentials (approximately 80 mV). However, at more depolarized potentials (approximately 55 mV), D₁ agonists enhanced evoked activity. At these potentials, D₁ agonists or cAMP analogs prolonged or induced slow subthreshold depolarizations and increased the duration of barium- or TEA-induced Ca²⁺-dependent action potentials. Both effects were blocked by L-type Ca²⁺ channel antagonists (nicardipine, calciseptine) and were occluded by the L-type channel agonist BayK 8644arguing that the D₁ receptor-mediated effects on evoked activity at depolarized membrane potential were mediated by enhancement of L-type Ca²⁺ currents. These results reconcile previous in vitro and in vivo studies by showing that D₁ dopamine receptor activation can either inhibit or enhance evoked activity, depending on the level of membrane depolarization.

Key words: dopamine; neuromodulation; firing patterns; calcium; neostriatum, basal ganglia

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