Changes in the extracellular environment during development, maturation, and injury. The extracellular environment is modified and sculpted during development in an activity- and experience-dependent manner. This gives rise to a mature and refined neuronal network in adulthood. The somatodendritic (I) and axonal (II) compartments are modified by different molecules and cells in the extracellular environment. I. (a) During development, ECM molecules such as CSPGs, tenascins, and semaphorins are upregulated. Growth-promoting factors are also expressed by neurons. These molecules aid synaptic plasticity through sprouting, growth, guidance and formation of new contacts. (b) As the CNS matures, synapses are pruned and only functionally relevant synapses are retained in adulthood. Components of the ECM, coalesce, forming PNNs around the cell body and proximal dendrites of neurons. This prevents new synapse formation and therefore limits plasticity. (c) After CNS injury, the same molecules that promoted growth during development now have inhibitory effects. CSPGs and semaphorins are upregulated, preventing growth cones forming new synaptic contacts leading to limited sprouting and plasticity. (d) The continuum of synaptic growth and plasticity increases during development but becomes limited in adulthood and further inhibited after injury. II. (e) During development, growth cones extend from unmyelinated axons to form new synaptic contacts. This is mediated by molecules that promote growth such as semaphorins, tenascins, and integrins; thus, plasticity and growth are favoured. (f) As the CNS matures, (adulthood) oligodendrocytes form mature myelin sheaths containing MAIs (Nogo-A, MAG, and OMgp), restricting aberrant sprouting. Astrocytes secrete CSPGs to limit structural plasticity. Growth-promoting proteins such as integrins and their ECM ligands (tenascins) are downregulated and absent in the axon. These factors maintain a stable environment. (g) After CNS injury, CSPGs and semaphorins are upregulated, preventing new growth cones from connecting to targets, leading to dystrophic end bulbs. Reactive astrocytes form a glial scar at the site of injury, preventing regeneration of damaged axons. Myelin debris and MAIs released from damaged myelin sheaths inhibit sprouting, axonal extension, and regeneration. Tenascin is upregulated without a concomitant upregulation of its growth-promoting integrin receptor, alpha9beta1. As such after injury, the CNS environment is not conducive to repair and regeneration. (h) The continuum of axonal growth increases during development, becomes stable in adulthood but is significantly impaired/inhibited after injury.