Multisecond oscillations in firing rate in the basal ganglia: Robust modulation by dopamine receptor activation and anesthesia

Studies of CNS electrophysiology have suggested an important role for oscil latory neuronal activity in sensory perception, sensorimotor integration, a nd movement timing. In extracellular single-unit recording studies in awake , immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus tit = 15, globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly period ic. Significant activity in power spectra tin the 2- to 60-s range of perio ds from basal spike trains was found for 56% of neurons in these three nucl ei. Spectral peaks corresponded to oscillations with mean periods of simila r to 30 s in each nucleus. Multisecond baseline oscillations were also foun d in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apo morphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscilla tions, increasing oscillatory frequency (means of spectral peak periods wer e reduced to similar to 15 s) and increasing the regularity of the oscillat ions. Apomorphine effects on oscillations in firing rate were more consiste nt from unit to unit than were its effects on mean firing rates in the ento peduncular nucleus and substantia nigra. Apomorphine modulation of multisec ond periodic oscillations was reversed by either D-1, or D-2, antagonists a nd was mimicked by the combination of selective D-1, (SKF-81297) and D-2, ( quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Mul tisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ga nglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognit ive processes that are affected by dopamine. Periodic firing rate oscillati ons in basal ganglia output nuclei should strongly affect the firing patter ns of target neurons and are likely involved in coordinating neural activit y responsible for motor sequences. Modulation of slow, periodic oscillation s in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states.