Permissive proteolytic activity for visual cortical plasticity

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Tissue-type plasminogen activator (tPA) regulates extracellular proteolytic cascades.
• Experience-dependent plasticity in the visual cortex is critical during development.
• Ocular dominance plasticity is impaired in GAD65 knockout mice due to reduced GABAergic transmission.

Purpose of the Study:

• To investigate the role of tPA signaling in experience-dependent plasticity of the mouse visual cortex.
• To determine if tPA activity is modulated by monocular deprivation (MD).
• To explore the relationship between tPA, GABAergic signaling, and visual cortical plasticity.

Main Methods:

• Monocular deprivation (MD) in wild-type and GAD65 knockout mice.
• Measurement of tPA proteolytic activity in the visual cortex.
• Assessment of ocular dominance plasticity and neuronal responsiveness.
• Gene dose-dependent rescue and direct tPA infusion experiments.

Main Results:

• tPA activity increased in the visual cortex within 2 days of MD.
• This tPA regulation failed in GAD65 knockout mice, correlating with impaired plasticity.
• Mice lacking tPA showed suppressed loss of responsiveness to the deprived eye despite normal neuronal activity.
• Plasticity was restored by increasing tPA levels via gene dose or infusion.

Conclusions:

• tPA signaling is essential for experience-dependent plasticity in the developing visual cortex.
• tPA activity is regulated by sensory experience and linked to the excitatory-inhibitory balance.
• tPA may couple functional and structural changes, mediating neurite outgrowth after sensory deprivation.