2006 Fiscal Year Final Research Report Summary
The role of serine proteases in synaptic plasticity of mouse visual cortex
| Project/Area Number |
16500211
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
MATAGA Nobuko RIKEN, Neuronal Circuit Development, Research Specialist, 神経回路発達研究チーム, 専門職研究員 (20209464)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Visual Cortex / Synaptic Plasticity / Monocular Deprivation / Morphological Changes / Spine Pruning / Knockout Mice / Plasminogen Activator / Extracellular Matrix |
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| Research Abstract |
Sensory experience physically rewires the brain in early postnatal life through unknown processes.
1) We identified a robust anatomical consequence of monocular deprivation (MD) in layer 2/3 of visual cortex that corresponds to the rapid, functional loss of responsiveness preceding any changes in axonal input. Protrusions on pyramidal cell apical dendrites increased steadily after eye-opening, but were transiently lost through competitive mechanisms after brief MD during the physiological critical period. Proteolysis by tissue-type plasminogen activator (tPA) conversely declined with age and increased upon MD only in young mice. Targeted disruption of tPA release or its upstream regulation by glutamic acid decarboxylase (GAD65) prevented spine loss by MD that was pharmacologically rescued concomitant with critical period plasticity.
2) To explore correspondingly rapid and local pre-synaptic refinements by sensory deprivation, excitatory intracortical or thalamocortical axon terminals wer
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e visualized in the BZ by vesicular glutamate transporters (vGlut)1 and vGlut2, respectively. The immunoreactivity of vGlut2 decreased around layer IV by brief monocular deprivation (4dMD) during the CP. Interestingly, both signals in all layers were lower in the contralateral BZ to the closed eye than that in the ipsilateral BZ by TTX injections, that induces stronger effect in functional shifts and rapid dendritic refinement compared to 4dMD. These results suggest that rapid and local functional loss of excitatory inputs may correlate with dendritic spine pruning by experience-dependent competition.
3) We examined a specific role for tPA upon the extracellular matrix (ECM). Perineuronal nets bound to wisteria floribunda agglutinin (WFA) appeared normally in adult wild-type (WT) and tPA KO mice, primarily in layer IVN of the binocular zone (BZ).
4) We explored potential substrates for tPA-mediated proteolysis in mouse visual cortex. Limited proteolysis of extracellular proteins was observed in a dose-and time-dependent manner by active enzyme plasmin. Less
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