Bidirectional synaptic plasticity in response to single or paired pulse activation of NMDA receptors.
It is still incompletely known how NMDA receptors (NMDA-R) regulate bidirectional synaptic plasticity. We examined this issue by an experimental protocol in which paired pulse stimulation (PPS) with 50ms interstimulus interval and basal frequency of 0.1Hz was applied to CA1 area of rat hippocampal slices during low Mg(2+) perfusion. Under blockade of NMDA-Rs by AP5, PPS for 12-60min led to only a minor depression. In contrast, when PPS was applied in the absence of AP5, there was a prominent short-term potentiation (STP), mainly of AMPA-R mediated responses, with peak at 1min and lasting 10-15min. The STP was followed by a slowly developing long-term depression (LTD). Applying AP5 during the STP, converted it to a stable increase relative to the control pathway. Following peak STP, plasticity was controlled in a composite manner. Whereas the initial decay was counteracted by NMDA-R activation, the following LTD was dependent on such activation. Our data suggest that synaptic changes do not only depend on the instantaneous, NMDA-dependent Ca(2+) concentration in the dendritic spine, but are also influenced by prior induction events. In addition to NMDA-R driven processes, passive relaxation contributes to the synaptic plasticity and in some cases outbalances the active control.
Huang
Fen-Sheng
FS
Department of Medical Biophysics, Institute of Neuroscience and Physiology, University of Gothenburg, Box 433, 40530 Gothenburg, Sweden. fs.huang@physiol.gu.se <fs.huang@physiol.gu.se>
Abbas
Abdul-Karim
AK
Li
Rui
R
Afanasenkau
Dzmitry
D
Wigström
Holger
H
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D014633:Valine