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Bargas, J; Galarraga, E; HernandezLopez, S; Surmeier, DJ; Reyes, A (1997)

D-1 RECEPTOR ACTIVATION ENHANCES EVOKED DISCHARGE IN NEOSTRIATAL MEDIUM SPINY NEURONS BY MODULATING AN L-TYPE CA2+ CONDUCTANCE

J NEUROSCI 17(9):3334-3342
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Most in vitro studies of D-1 dopaminergic modulation of excitability in neostriatal medium spiny neurons have revealed inhibitory effects. Yet studies made in more intact preparations have shown that D-1 receptors can enhance or inhibit the responses to excitatory stimuli. One explanation for these differences is that the effects of D-1 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 D-1 receptor stimulation at depolarized and hyperpolarized membrane potentials. As previously reported, evoked discharge was inhibited by D-1 agonists when holding at negative membrane potentials (approximately -80 mV). However, at more depolarized potentials (approximately -55 mV), D-1 agonists enhanced evoked activity. At these potentials, D-1 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 8644-arguing that the D-1 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 D-1 dopamine receptor activation can either inhibit or enhance evoked activity, depending on the level of membrane depolarization.