Bilateral effects of unilateral intrastriatal GDNF on locomotor-excited and nonlocomotor-related striatal neurons in aged F344 rats.
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.
Stanford
John A
JA
Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. jstanford@kumc.edu
Salvatore
Michael F
MF
Joyce
Barry M
BM
Zhang
Hongyu
H
Gash
Don M
DM
Gerhardt
Greg A
GA
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D007263:Infusions, Parenteral; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
D051100:Glial Cell Line-Derived Neurotrophic Factor