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. 2013 Jan;224(1):15-24. doi: 10.1007/s00221-012-3285-3. Epub 2012 Oct 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Adrenergic Agents / toxicity*
  • Animals
  • Brain Injuries / chemically induced*
  • Dyskinesia, Drug-Induced / physiopathology
  • Forelimb / physiopathology
  • Functional Laterality / drug effects*
  • Functional Laterality / physiology
  • Male
  • Medial Forebrain Bundle / injuries
  • Neurons / physiology*
  • Oxidopamine / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / pathology*
  • Time Factors

Substances

  • Adrenergic Agents
  • Oxidopamine