Brain extracellular space: developmental studies in rat optic nerve.

Analysis of neural activity-dependent fluctuations in K+, H+, and ECS dimensions in the developing RON has revealed major changes during the first two to three postnatal weeks. The emergence of the adult ceiling level for evoked extracellular K+ (10 to 12 mM) and significant ECS shrinkage are roughly correlated in time with the proliferation and maturation of glial cells in this structure. This observation and others have led to the hypothesis that ECS shrinkage depends upon electrolyte and water transport into glial cells with subsequent swelling. Development of the adult K+ ceiling level may also depend upon glial cells, but it is likely that other factors contribute to this homeostatic mechanism. Marked alterations in activity-dependent pHo shifts were seen with development and may be related to changes in the activity of carbonic anhydrase in this structure. The technological means are at hand to pursue these questions vigorously in an effort to provide further insight into the mechanisms of ionic and fluid homeostasis of brain ECS, and the developing RON appears to be a useful model system in this regard.