Frequency-dependent requirement for calcium store-operated mechanisms in induction of homosynaptic long-term depression at hippocampus CA1 synapses.
For induction of long-term depression (LTD), mechanisms dependent on N-methyl-D-aspartate receptors (NMDARs) and on intracellular calcium stores have been separately known. How these two mechanisms coexist at the same synapses is not clear. Here, induction of LTD at hippocampal Schaffer collateral-to-CA1 pyramidal cell synapses was shown to depend on NMDARs throughout the theoretically predicted activation range for LTD induction. With stimulation at 1 Hz, the largest LTD was induced in a store-independent manner. With stimulation at 0.5 and 2.0 Hz the induced LTD was much smaller, and dependence on calcium stores appeared. Under caffeine application, an enlarged LTD was induced with 0.5 Hz stimulation. Postsynaptic blockade of ryanodine receptors prevented this caffeine-induced enhancement of LTD. It is therefore suggested that calcium release from calcium stores facilitated by caffeine contributed to the LTD enhancement, and that the caffeine effect was exerted on the postsynaptic side. Induction of this enhanced LTD was resistant to NMDAR blockade. We thus propose that the store-dependent mechanism for LTD induction is dormant at the centre of the theoretically predicted activation range for LTD induction, but operates at the fringes of this activation range, with its contribution more emphasized when ample calcium release occurs.
Nakano
Makoto
M
Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Yamada
Shin-ichiro
S
Udagawa
Rie
R
Kato
Nobuo
N
D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D019284:Thapsigargin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D012430:Ruthenium Red; D012433:Ryanodine; D002110:Caffeine; D019284:Thapsigargin; D016291:Dizocilpine Maleate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D002118:Calcium; C000543:cyclopiazonic acid