Multisecond oscillations in the subthalamic nucleus: effects of apomorphine and dopamine cell lesion

Abstract

Clinical and preclinical data indicate that the subthalamic nucleus (STN) plays a critical role in mediating the hyper- and hypoactive behavioral states associated with increases and decreases in dopamine receptor stimulation in the basal ganglia. The present study investigates effects of dopamine receptor stimulation on slow multisecond oscillations in firing rates in STN neurons. Extracellular, single-unit recordings were performed in locally anesthetized and immobilized rats which were either intact or had received unilateral 6-OHDA lesions of the medial forebrain bundle. The majority (64%) of spike trains recorded from STN neurons exhibited periodic oscillations in firing rate within the range of 2-60 sec, with an average period of 24 sec. The distribution of these baseline periodicities was not altered by unilateral 6-OHDA lesion, but periods were significantly shortened by systemic administration of the D1/D2 agonist apomorphine. This effect was observed in a greater proportion of neurons recorded from 6-OHDA-lesioned rats as compared to intact rats, was notably diminished in rats systemically anesthetized with chloral hydrate, and did not correlate with drug-induced changes in firing rate. These oscillations are similar to slow periodicities in firing rate recently reported in other basal ganglia nuclei. The possibility that these periodic oscillations in firing rate play a significant role in basal ganglia function was supported by the observation that the time of onset of apomorphine induced alterations in amplitude and periodicity of slow oscillations in STN spike trains is coincident with the onset of behavioral effects of this drug in 6-OHDA-lesioned animals. Synapse 38:38-50, 2000. Published 2000 Wiley-Liss, Inc.