Fig. 3.

Developmental timeline of neuronal activity and BBB/BRB maturation in the mouse CNS. Developmental timeline of synaptogenesis, neural activity and BBB/BRB maturation in the mouse cerebral cortex (A) and retina (B). (A) Synaptogenesis (light-gray bar) in the mouse cortex begins around E13.5 (E16.5 is when activity-dependent synaptic pruning begins), whereas activity-dependent synaptic pruning (dark-gray bar) begins at E16.5 and peaks at birth. Both processes continue through P21. The transcellular barrier properties of the BBB (blue curve) in the cortex do not completely mature until E16-E17, and the paracellular BBB properties (pink curve) do not mature until birth, when the transendothelial electrical resistance (TEER) is highly increased. (B) Between E16 and P0, retinal waves (gray bars) are propagated by gap junctions (stage I). From P0-P10, these waves are cholinergic in nature (stage II), whereas between P10-P14 they switch to being glutamatergic (stage III). Most neuronal activity (dark-gray bars) in the mouse retina after P14 is light mediated (i.e. photoreceptor dependent), although some reports suggest that photoreceptor activity occurs as early as P10. Moreover, the light response by intrinsically photosensitive melanopsin ganglion cells occurs throughout this period (E16-adult). By P10, the endothelial transcellular BRB (pink curve) is mature throughout all retinal vascular beds. In contrast, the paracellular BRB (blue curve) properties of the retinal vasculature gradually arise until P18.