Regressive and proliferative processes in the formation of cortico-spinal projection.
Project/Area Number |
20300138
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurophysiology and muscle physiology
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Research Institution | Teikyo University |
Principal Investigator |
SAKURAI Masaki Teikyo University, 医学部, 教授 (30162340)
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Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2009: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2008: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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Keywords | 皮質脊髄投射 / シナプス形成 / シナプス除去 / NMDA受容体 / GluN2B / 皮質脊髄路 / 運動感覚皮質 / 皮質脊髄シナプス / GluN2A / GluRε2(NR2B) / 軸索退縮 / 軸索自切 / 軸索変性 |
Research Abstract |
We developed corticospinal projection system in vitro using slice co-cultures of rodent sensorimotor cortex and spinal cord, where we found thatcorticospinal (CS) synapses are formed diffusely in the spinal gray matter until 7 DIV butthose on the ventral side are eliminated later until 14 DIV in an NMDA receptor-dependent manner. In the present studies : (1) We labeled CS axons with EYFP transfected with electroporation and studied axonal regression from ventral side on long-term live imaging. There were three types of regressive events : retraction, amputation (autaxotomy), and degeneration. We analyzed their character in detail. (2) We co-cultured slices obtained from GluN2B or GluN2A KO mice and wild type animals. The synapse elimination was not seen when GluN2B KO spinal cord was cocultured with wild type cortex, indicating that postsynaptic (not presynaptic) GluN2B (rather than GluN2A) is essentially involved in the synapse elimination. Furthermore, differential effect of 2B and 2A seems to be downstream signaling rather than the difference in amount of Ca entry. (3) We studied developmentalchange in distribution of CS cells projecting to a single segment, C7, by injecting almost entire half gray matter of C7 at P7 and P56. At P7, projecting cells are widely distributed through motor-related cortex and somatosensory cortices, which was dramtically decreased in density at P56. This reduction was not due to cell death but axon elimination. (4) Wefound direct cortico-motoneuronal synapses at P7 rat by recording CS-EPSC from identified motoneuron retrogradely labeled with CTB. Only motoneurons innervate distal limb muscles received direct CS synapses.
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Report
(4 results)
Research Products
(48 results)