The phospholipid mediator platelet-activating factor mediates striatal synaptic facilitation.
The phospholipid mediator platelet-activating factor (PAF), an endogenous modulator of glutamatergic neurotransmission, can also be secreted by brain mononuclear phagocytes during HIV-1 infection. Platelet-activating factor can induce neuronal apoptosis by NMDA receptor-dependent and independent mechanisms. We now demonstrate that acute administration of sublethal doses of PAF to striatal slices augments synaptic facilitation in striatal neurons following high-frequency stimulation, which can be blocked by PAF receptor antagonists, suggesting that striatal synaptic facilitation can be augmented by PAF receptor agonism. We also demonstrate that repeated sublethal doses of PAF during tetanic stimulation can greatly increase the magnitude of postsynaptic potentials and action potentials, but a lethal dose of PAF destroys the capacity of corticostriatal synapses to achieve this augmented synaptic facilitation. Thus, the relative concentration and temporal pattern of PAF expression at glutamatergic synapses may govern whether it acts in a physiologic or pathophysiologic manner during striatal neurotransmission.
Center for Aging and Developmental Biology, Aab Biomedical Institute, University of Rochester Medical Center, Box 645, 601, Elmwood Avenue, Rochester, NY 14642, USA. Pat_Lu@urmc.rochester.edu
Shao-Ming
SM
Lu
Ning
N
Tong
Harris A
HA
Gelbard
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000502:physiology* / Q000633:toxicity; D010972:Platelet Activating Factor / Q000819:agonists / Q000502:physiology* / Q000633:toxicity; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D010743:Phospholipids; D010972:Platelet Activating Factor