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Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator
Nobuko Mataga1, Yoko Mizuguchi, Takao K Hensch
1Laboratory for Neuronal Circuit Development, Institute of Physical and Chemical Research (RIKEN), Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Neuron
|December 18, 2004
Summary
Sensory experience reshapes the brain during development. Monocular deprivation in young mice caused transient spine loss in the visual cortex, linked to tissue-type plasminogen activator (tPA) activity.
Area of Science:
- Neuroscience
- Developmental Biology
- Visual System Plasticity
Background:
- Early sensory experiences are crucial for brain development and function.
- The precise mechanisms by which sensory input physically alters brain structure, particularly in the visual cortex, remain incompletely understood.
- Monocular deprivation (MD) is a key experimental paradigm to study visual system plasticity.
Purpose of the Study:
- To identify the anatomical and molecular mechanisms underlying structural changes in the visual cortex following monocular deprivation during the critical period.
- To investigate the role of proteolysis and specific molecular players in experience-dependent structural remodeling.
Main Methods:
- Utilized monocular deprivation (MD) in young mice during the critical period of visual development.
- Examined structural changes in pyramidal cell apical dendrites in layer II/III of the visual cortex using microscopy.
- Assessed the activity and expression of tissue-type plasminogen activator (tPA) and glutamic acid decarboxylase (GAD65).
- Employed genetic and pharmacological interventions to disrupt or rescue tPA function and GAD65 regulation.
Main Results:
- Monocular deprivation (MD) during the critical period induced a transient loss of dendritic spines on pyramidal cells in the visual cortex.
- This spine loss occurred rapidly and preceded changes in axonal input, suggesting an intrinsic competitive mechanism.
- Proteolysis mediated by tissue-type plasminogen activator (tPA) was found to be age-dependent and increased with MD in young mice.
- Disrupting tPA release or GAD65 regulation prevented MD-induced spine loss, which could be rescued pharmacologically.
Conclusions:
- Identified an extracellular proteolytic mechanism involving tPA that mediates experience-dependent structural remodeling in the developing visual cortex.
- Demonstrated that GAD65 regulates tPA activity, linking neurotransmission to structural plasticity.
- Established a link between early sensory experience, structural remodeling in the binocular zone, and the establishment of visual function.