CREB-Dependent Differential Complement Regulator Positioning for Activity-Based Synaptic Vulnerability Control

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This hypothesis proposes that the CREB-BDNF-TrkB activity-dependent signaling cascade directly controls the spatial positioning and expression levels of complement regulators CD55 and CD46 on synaptic membranes, creating an activity-based tagging system for synaptic elimination. High-frequency neural activity triggers calcium influx and CaMKIV/PKA-mediated CREB1 phosphorylation at serine 133, whic