| 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 |
| 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
| Author | Title of Article | |||
| Hori, Y. et al. | Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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. | |||
| Journal | Volume | Year | Pages Concerned | |
| J. Physiol. | 509 | 1998 | 419-423 | |
| Author | Title of Article | |||
| Manabe, T. et al. | Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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. | |||
| Journal | Volume | Year | Pages Concerned | |
| 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 | |||