Bilateral effects of unilateral intrastriatal GDNF on locomotor-excited and nonlocomotor-related striatal neurons in aged F344 rats

Neurobiol Aging. 2007 Jan;28(1):156-65. doi: 10.1016/j.neurobiolaging.2005.10.015. Epub 2005 Nov 28.

Abstract

In order to determine its effects on locomotor-related striatal electrophysiology in aged rats, glial cell line-derived neurotrophic factor (GDNF) was infused (vehicle or 30mug) into the right striatum of 24-25-month-old Fischer 344 (F344) rats. Multi-wire electrode arrays were then chronically implanted in striatum bilaterally. Thirty days later, striatal electrophysiological activity was recorded during freely moving conditions. Individual neurons were classified as locomotor-excited if they exhibited significant increases in firing rates during locomotor bouts versus periods of nonmovement. GDNF produced a significant increase in overall firing rates in locomotor-excited striatal neurons. This effect was observed in both the infused and the contralateral striatum. GDNF also attenuated the bursting activity of nonlocomotor-related striatal neurons, an effect that was also present bilaterally. These results suggest that GDNF's antiparkinsonism effects are associated with increased excitability of motor-related striatal neurons and diminished activity of neurons that do not exhibit explicit motor-related changes in activity. Such studies may aid in understanding the mechanism of potential therapies for movement disorders seen in aging and Parkinson's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / physiology*
  • Animals
  • Biological Clocks / drug effects
  • Biological Clocks / physiology*
  • Corpus Striatum
  • Glial Cell Line-Derived Neurotrophic Factor / administration & dosage*
  • Infusions, Parenteral
  • Locomotion / drug effects
  • Locomotion / physiology*
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Rats
  • Rats, Inbred F344

Substances

  • Glial Cell Line-Derived Neurotrophic Factor