Activation of inositol 1,4,5-trisphosphate receptors during preconditioning low-frequency stimulation suppresses subsequent induction of long-term potentiation in hippocampal CA1 neurons.
We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated during preconditioning low-frequency stimulation (LFS) in the subsequent high-frequency stimulation (HFS)-induced induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential (EPSP) or the population spike (PS) by delivery of HFS (a tetanus of 100 pulses at 100 Hz) to the Schaffer collateral-commissural pathway to CA1 neuron synapses was suppressed when the CA1 synapses were preconditioned by LFS of 1000 pulses at 1 Hz. This effect was inhibited when the preconditioning LFS was applied in the presence of an N-methyl-D-aspartate receptors (NMDARs) antagonist, a metabotropic glutamate receptor (mGluR) antagonist, IP3R antagonist, a calmodulin-dependent kinase II inhibitor or a calcineurin inhibitor. Furthermore, blockade of group I mGluRs immediately before the delivery of HFS blocked the inhibitory effect of the preconditioning LFS on subsequent induction of LTP by HFS. These results suggest that, in hippocampal CA1 neuron synapses, co-activation of NMDARs and IP3Rs during a preconditioning LFS results in both phosphorylation and dephosphorylation events that lead to prolonged activation of group I mGluRs that is responsible for the failure of LTP induction.
Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
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Yamazaki
Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan; Laboratory for Developmental Neurobiology, Riken Brain Science Institute, Wako, Saitama 351-0198, Japan. Electronic address: sfujii@med.id.yamagata-u.ac.jp.
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Fujii
Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan; Laboratory for Developmental Neurobiology, Riken Brain Science Institute, Wako, Saitama 351-0198, Japan.
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JI
Goto
Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
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Fujiwara
Laboratory for Developmental Neurobiology, Riken Brain Science Institute, Wako, Saitama 351-0198, Japan.
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Mikoshiba
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
D053496:Inositol 1,4,5-Trisphosphate Receptors; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium
CA1 synapses; IP(3) receptors; LTP; LTP suppression; calcineurin; preconditioning