Pathological synaptic plasticity in the striatum: implications for Parkinson's disease

Neurotoxicology. 2005 Oct;26(5):779-83. doi: 10.1016/j.neuro.2005.02.002. Epub 2005 May 31.

Abstract

Repetitive stimulation of the corticostriatal pathway can cause either a long-lasting increase, or an enduring decrease in synaptic strength, respectively referred to as long-term potentiation (LTP), and long-term depression (LTD), both requiring a complex sequence of biochemical events. Once established, LTP can be reversed to control levels by a low-frequency stimulation (LFS) protocol, an active phenomenon defined "synaptic depotentiation", required to erase redundant information. In the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD), striatal synaptic plasticity has been shown to be impaired, though chronic treatment with l-dopa was able to restore it. Interestingly, a consistent number of l-dopa-treated animals developed involuntary movements, resembling human dyskinesias. Strikingly, electrophysiological recordings from the dyskinetic group of rats demonstrated a selective impairment of synaptic depotentiation. This survey will provide an overview of plastic changes occurring at striatal synapses. The potential relevance of these findings in the control of motor function and in the pathogenesis both of Parkinson's disease and l-dopa-induced motor complications will be discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use
  • Cerebral Cortex / physiopathology
  • Denervation
  • Dyskinesia, Drug-Induced / physiopathology
  • Humans
  • Levodopa / adverse effects
  • Levodopa / therapeutic use
  • Long-Term Potentiation / physiology
  • Neostriatum / physiology*
  • Neostriatum / physiopathology*
  • Neuronal Plasticity / physiology*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / physiopathology*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / physiopathology
  • Rats
  • Synapses / physiology*

Substances

  • Antiparkinson Agents
  • Levodopa