Summary of Research Project Results Under the JSPS FY2000
"Research for the future Program"



1.Research Institution University of Tokyo
 
2.Research Area Life Science
 
3.Research Field Higher Brain Functions
 
4.Term of Project FY1996〜FY2000
 
5.Project Number 96L00205
 
6.Title of Project Molecular Mechanisms of Central Synaptic Modulation Underlying Memory Formation

7.Projetct Leader
Name Institution,Department Title of Position
Tomoyuki Takahashi University of Tokyo Graduate School of Medicine Professor

8.Core Members

Names Institution,Department Title of Position
Toshiya Manabe University of Tokyo Graduate School of Medicine lecturer
Kayoko Onodera University of Tokyo Graduate School of Medicine lecturer
Tetuhiro Tsujimoto University of Tokyo Graduate School of Medicine lecturer

9.Cooperating Researchers

Names Institution,Department Title of Position
Katsunori Kobayasi University of Tokyo Graduate School of Medicine research associate
Naoto Saitou University of Tokyo Graduate School of Medicine research associate
Taro Ishikawa University of Tokyo Graduate School of Medicine graduate student

10.Summary of Research Results

(1) During postnatal development Ca channel subtypes switch from N,R,P/Q type to predominant P/Q type at the brainstem excitatory, thalamic inhibitory and cerebellar inhibitory synapses. In contrast no such switch was observed at spinal dorsal horn inhibitory and cerebral cortical synapses. (2) During postnatal development GABAA receptor α subunit was found to switch from α2 to α1, thereby speeding the decay time of inhibitory postsynaptic currents at the thalamic synapse. (3) Excitatory postsynaptic responses conveyed by primary sensory C-fibers were recorded from neurons in trigeminal caudal nucleus in brainstem of rats. These responses underwent transient facilitation during repetitive stimulation and expressed long-term potentiation upon tetanic conditioning stimulation. The mechanism of LTP induction was suggested to be presynaptic and mediated by metabotropic glutamate receptors. (4) By injecting guanine nucleotide analogues into a giant nerve terminals in the rat brain stem slice, the principal role of presynaptic G proteins was identified to be the speeding of the replenishment of synaptic vesicles depleted by high frequency transmission. (5) The GABAA receptor agonist muscimol was found to activate GABAB receptor at the nerve terminal, thereby causing presynaptic inhibition. (6) Cyclothiazide known to block postsynaptic AMPA receptor desensitization was found to suppress presynaptic potassium channels, thereby facilitating transmitter release.

11.Key Words

(1)Postnatal development、(2)synapse、(3)calcium channel
(4)GABA receptor、(5)primary afferent synapse、(6)pain
(7)Long-term potentuiation、(8)Metabotropic glutamate receptors、(9)G protein

12.References

[Reference Articles]
Author Title of Article
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J. Physiol. (London) 492 1996 867-876

Author Title of Article
Silver, R. A. et al. Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites.
Journal Volume Year Pages Concerned
J. Physiol. (London) 494 1996 230-250

Author Title of Article
Takahashi, T. et al. Functional Correlation of NMDA recepter ε subunits expression with the properties of single-channel and synaptic current in the developing cerebellum.
Journal Volume Year Pages Concerned
J. Neurosci. 16 1996 4376-4382

Author Title of Article
Yokoi, M. et al. Impairment of hippocampal mossy fiber LTD in mice lacking metabotropic glutamate receptor subtype 2.
Journal Volume Year Pages Concerned
Science 273 1996 645-647

Author Title of Article
Kobayashi, K. et al. Presynaptic long-term depresssion at the hippocampal mossy fiber-CA3 synapse.
Journal Volume Year Pages Concerned
Science 273 1996 648-650

Author Title of Article
Takahashi, T. et al. Presynaptic calcium current modulation by a metabotropic glutamate receptor.
Journal Volume Year Pages Concerned
Science 274 1996 594-597

Author Title of Article
Hayashi, Y. et al. Calcium-and calmodulin-dependent phosphorylation of AMPA type glutamate receptoer subunits by endogenous protein kinases in the postsynaptic density.
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Mol. Br. Res. 46 1997 338-342

Author Title of Article
Forsythe, I. D.et al. Inactivation of presynaptic calcium current contribute to synaptic depression at a fast central synapse.
Journal Volume Year Pages Concerned
Neuron 20 1998 797-807

Author Title of Article
Takahashi, T. et al. G-protain-coupled modulation of presynaptic calcium currents and transmitter release by a GABAB receptor.
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J. Neurosci. 18 1998 3138-3146

Author Title of Article
Iwasaki, S. et al. Developmental changes in calcium channel types mediating synaptic transmission in rat auditory brainstem.
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Author Title of Article
Manabe, T. et al. Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors.
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Nature 394 1998 577-581

Author Title of Article
Mori, H. et al. Role of the carboxyl-terminal region of the GluRε 2 subunit in synaptic localization of the NMDA receptor channel.
Journal Volume Year Pages Concerned
Neuron 21 1998 571-580

Author Title of Article
Cuttle, M. F. et al. Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem.
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J. Physiol. 512 1998 723-729

Author Title of Article
Hori, T. et al. Presynaptic mechanism for phorbol ester- induced synaptic potentiation.
Journal Volume Year Pages Concerned
J. Neurosci. 19 1999 7262-7267

Author Title of Article
Kobayashi, K. et al. Platelet-activating factor receptor is not required for long-term potentiation in the hippocampal CA1 region.
Journal Volume Year Pages Concerned
Eur. J. Neurosci. 11 1999 1313-1316

Author Title of Article
Kobayashi, K. et al. Calcium-dependent mechanisms involved in presynaptic long-term depression at the hippocampal mossy fibre-CA3 synapse.
Journal Volume Year Pages Concerned
Eur. J. Neurosci. 11 1999 1633-1638

Author Title of Article
Terada, S. et al. Impairement of inhibitory synaptic transmission in mice lacking synapsin 1.
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J. Cell Biol. 145 1999 1039-1048

Author Title of Article
Sakaguchi, G. et al. Doc2α is an activity-dependent modulator of excitatory synaptic transmission.
Journal Volume Year Pages Concerned
Eur. J. Neurosci. 11 1999 4262-4268

Author Title of Article
Iwasaki, S. et al. Developmental changes in calcium channel types mediating central synaptic transmission.
Journal Volume Year Pages Concerned
J. Neurosci. 20 2000 59-65

Author Title of Article
Okada, Y. et al. Functional correlation of GABAA Receptor a subunits expression with the properties of IPSCs in the developing thalamus.
Journal Volume Year Pages Concerned
J. Neurosci. 20 2000 2202-2208

Author Title of Article
Hamba, M. et al. Long-term potentiation of primary afferent neurotransmission at trigeminal synapses of juvenile rats.
Journal Volume Year Pages Concerned
Eur. J. Neurosci. 12 2000 1128-1134

Author Title of Article
Onodera, K. et al. Primary afferent synaptic responses recorded from trigeminal caudal neurons in a mandibular nerve-brainstem preparation of neonatal rats.
Journal Volume Year Pages Concerned
J. Physiol. 524 2000 503-512

Author Title of Article
Takahashi, T. et al. The role of GTP-binding protein activity in fast central synaptic transmission.
Journal Volume Year Pages Concerned
Science 289 2000 460-463

Author Title of Article
Yamauchi, T. et al. Presynaptic inhibition by muscimol through GABAB receptors.
Journal Volume Year Pages Concerned
Eur. J. Neurosci. 12 2000 3433-3436

Author Title of Article
Ishikawa, T. et al. Mechanisms underlying presynaptic facilitatory of cyclothiazede at the calyx of Held of juvenile rats.
Journal Volume Year Pages Concerned
J. Physiol., in press   2001  

Author Title of Article
Futai, K. et al. High-fidelity transmission acquired through a developmental decrease in NMDA receptor expression at an auditory synapse.
Journal Volume Year Pages Concerned
J. Neurosci. in press   2001  


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