Role of Striatum in the Pause and Burst Generation in the Globus Pallidus of 6-OHDA-Treated Rats

Hitoshi Kita,Takako Kita

doi:10.3389/fnsys.2011.00042

Abstract

Electrophysiological studies in patients and animal models of Parkinson's disease (PD) often reported increased burst activity of neurons in the basal ganglia. Neurons in the globus pallidus external (GPe) segment in 6-hydroxydopamine (6-OHDA)-treated hemi-parkinsonian rats fire with strong bursts interrupted by pauses. The goal of this study was to evaluate the hypothesis that dopamine (DA)-depletion increases burst firings of striatal (Str) neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe and its projection sites. To evaluate this hypothesis, the unitary activity of Str and GPe was recorded from control and 6-OHDA-treated rats anesthetized with 0.5–1% isoflurane. The occurrence of pauses and bursts in the firings of GPe neurons was significantly higher in 6-OHDA than in normal rats. Muscimol injection into the Str of 6-OHDA rats increased average firing rate and greatly reduced the pauses and bursts in GPe. Recordings from Str revealed that most of the presumed projection neurons in control rats have very low spontaneous activity, and even the occasional neurons that did exhibit spontaneous burst firings did so with an average rate of less than 2 Hz. In DA-depleted Str, neurons having stronger bursts and a higher average firing rate were encountered more frequently. Juxtacellular labeling revealed that most of these neurons were medium spiny neurons projecting only to GPe. Injection of a behaviorally effective dose of methyl-l-DOPA into the Str of 6-OHDA rats significantly increased the average firing rate and decreased the number of pauses of GPe neurons. These data validate the hypothesis that DA-depletion increases burst firings of Str neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe. These results suggest that treatment to reduce burst Str–GPe inhibitory inputs may help to restore some PD disabilities.

Highlights

IntroductionElectrophysiological observations made in patients and animal models of basal ganglia diseases reported various changes in the activity of basal ganglia neurons including abnormal firing patterns, increased bursts and pauses, and abnormal synchronized oscillations (Pan and Walters, 1988; Filion and Tremblay, 1991; Bergman et al, 1994; Ni et al, 2000; Soares et al, 2004; Wichmann and DeLong, 2006; Stefani et al, 2011)
The aims of the present analysis of globus pallidus external (GPe) neurons were first, to evaluate whether or not increased burst firings of GPe neurons in 6-OHDA rats can be seen under isoflurane anesthesia, validating experimental conditions, and second, to evaluate whether any increased bursts were accompanied by an increased occurrence of pauses in the firings
The GPe neurons included in this report were of the high frequency firing with pause type, which are the most common type found in GPe (DeLong, 1971)

Summary

Introduction

Electrophysiological observations made in patients and animal models of basal ganglia diseases reported various changes in the activity of basal ganglia neurons including abnormal firing patterns, increased bursts and pauses, and abnormal synchronized oscillations (Pan and Walters, 1988; Filion and Tremblay, 1991; Bergman et al, 1994; Ni et al, 2000; Soares et al, 2004; Wichmann and DeLong, 2006; Stefani et al, 2011). We hypothesize that the strong, irregular burst, and pause activity of GPe contributes greatly to the generation of irregular activity in neurons of the basal ganglia output nuclei, the internal segment of the globus pallidus (GPi), and the substantia nigra pars reticulata (SNr), which disables information processing capability at their projection sites in the thalamus and brainstem (Stefani et al, 2011)

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