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Short- and long-term unilateral 6-hydroxydopamine lesions in rats show different changes in characteristics of spontaneous firing of substantia nigra pars reticulata neurons

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Abstract

The unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle induces hemiparkinsonism in rats and is a well established animal model of Parkinson’s disease. In this study, we assessed the spontaneous activity of substantia nigra pars reticulata (SNr) neurons in unilateral 6-OHDA- or sham-treated rats. Extracellular single cell recordings revealed a bilaterally decreased firing rate in short-term 6-OHDA-lesioned rats (8–10 weeks post lesion) while no rate differences were evident in long-term lesioned animals (5–8 months post lesion) in vivo under chloral hydrate anaesthesia. However, firing pattern of the SNr neurons (indicated by interspike interval (ISI) histogram parameters: coefficient of variation, skewness and kurtosis) was significantly altered only after long-term lesion: 53.8 % of the recorded cells in the ipsilateral 6-OHDA-lesioned SNr fired in a bursting pattern (compared to 5.9–16.7 % in contralateral SNr or sham controls). Additionally, behavioural effects of the lesion were assessed 4 weeks post lesion by the forelimb adjusting stepping test. A decreased number of adjusting steps with the contralateral forepaw, as well as an increased performance with the ipsilateral paw was found for the 6-OHDA-lesioned rats as compared to sham controls. Furthermore, stepping values were negatively correlated with the ISI parameters after long-term lesion, while there were no correlations with the short-term groups. Firing rate was not correlated regardless of the time frame. In conclusion, long-term changes in firing pattern may represent a neuronal correlate of the 6-OHDA-induced hemiparkinsonism and may be useful for the interpretation of 6-OHDA-induced motor deficits and compensatory mechanisms as well.

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Acknowledgments

This study was partly supported by the VolkswagenStiftung (AZ I/78992). We thank Nadine Lettfuss for her careful reading of the manuscript and her valuable comments on it. The authors further thank Prof. Cornelius Schwarz for giving us valuable advice during the establishment of the electrophysiology setup in our laboratory. We thank Dr. Nora von Ameln for excellent help while doing the first steps with this technique.

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The authors declare that they have no conflict of interest.

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  1. Department of Neuropharmacology, Institute of Neurobiology, University of Tuebingen, Auf der Morgenstelle 28E, 72076, Tuebingen, Germany

    Sonja Seeger-Armbruster

  2. Elementorganic Chemistry, Neuropharmacology, University of Tuebingen, Auf der Morgenstelle 18A, 72076, Tuebingen, Germany

    Andreas von Ameln-Mayerhofer

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  1. Sonja Seeger-Armbruster
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Correspondence to Sonja Seeger-Armbruster.

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Seeger-Armbruster, S., von Ameln-Mayerhofer, A. Short- and long-term unilateral 6-hydroxydopamine lesions in rats show different changes in characteristics of spontaneous firing of substantia nigra pars reticulata neurons. Exp Brain Res 224, 15–24 (2013). https://doi.org/10.1007/s00221-012-3285-3

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