Multisecond oscillations in firing rate in the globus pallidus: Synergistic modulation by D1 and D2 dopamine receptors

The firing rates of many basal ganglia neurons recorded in awake rats oscil late at seconds-to-minutes time scales, and the D1/D2 agonist apomorphine h as been shown to robustly modulate these oscillations. The use of selective D1 and D2 antagonists suggested that both these receptor subfamilies are i nvolved in apomorphine's effects. In the present study, spectral analysis r evealed that baseline multisecond oscillations were significantly periodic in 71% of globus pallidus neurons. Baseline oscillations had a wide range o f periods within the analyzed range, with a population mean of 32 +/- 2 a. Administration of the D1 agonist SKF 81297 (6-chloroPB) at 1.0 or 5.0 mg/kg significantly changed these oscillations, reducing means of spectral peak periods to 14 to 16 s (i.e., increasing oscillatory frequency). This effect was attenuated by D2 antagonist pretreatment. The D2 agonist quinpirole di d not cause a significant population change in multisecond periodicities. T he strongest effects on multisecond periodicities occurred after combined t reatment with SKF 81297 and quinpirole. Low, ineffective doses of SKF 81297 and quinpirole, when combined, produced a significant increase in oscillat ory frequency. Also, when quinpirole was administered after an already effe ctive dose of SKF 81297, quinpirole shifted oscillations to an even faster range (typically to periods of <10 s). The dopaminergic control of multisec ond periodicities in globus pallidus firing rate demonstrates D1/D2 recepto r synergism, in that the effects of D1 agonists are potentiated by and part ially dependent on D2 receptor activity. Modulation of multisecond oscillat ions in firing rate represents a novel means by which dopamine can influenc e globus pallidus physiology.