title: Short- and long-term unilateral 6-hydroxydopamine lesions in rats show different changes in characteristics of spontaneous firing of substantia nigra pars reticulata neurons.
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.
authors.affiliation: Department of Neuropharmacology, Institute of Neurobiology, University of Tuebingen, Auf der Morgenstelle 28E, 72076 Tuebingen, Germany. sonja.s.armbruster@gmx.de
authors.forename: Sonja
authors.initials: S
authors.lastname: Seeger-Armbruster
authors.forename: Andreas
authors.initials: A
authors.lastname: von Ameln-Mayerhofer
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000473:pathology*; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine