Figure 8

Critical period plasticity according to the developmental stage of PV-cells. (A) Proposed bidirectional role of inhibitory circuits at the onset (red) and offset (blue) of the plasticity. (B) First, DZ activates persistent plasticity (low acuity of the deprived eye, red symbols) in T1 KO mice (DZ1, 0.29 ± 0.01 versus Veh, 0.54 ± 0.02, p < 0.0001, ANOVA). Second, DZ restricts the plasticity (high acuity of the deprived eye, blue symbols) (DZ2, 0.50 ± 0.03 versus DZ1, p < 0.0001, ANOVA). (C) VEP amplitudes of the first negative peak (left, mean ± SEM) and averaged VEP traces (right, for low or high spatial frequency) reveal an amblyopic effect on the deprived eye long after the first DZ injection from P24 in T1 KO mice (red line), and conversely, no effect after vehicle (Veh, black line) or additional DZ injection from P60 (blue line). (D) A schematic model for CS-Otx2 accumulation and PV-cell maturation. Initial emergence of CS and Otx2 (red arrow) promotes the onset of the critical period (CP), and then further accumulation (blue arrow) leads to the offset. In both steps, the interaction between CS and Otx2 is crucial for PV-cell function, which is substituted by DZ treatment. CS-attached aggrecan in PNNs (green) increases Otx2 uptake, and internalized Otx2 further promotes aggrecan expression in PV-cells (cartoon). This positive loop enhances the visual response and PV expression from the beginning of their weak properties and is finally involved in the inflexibility of this local circuitry (at post-CP). The plastic state (center) can be activated or inactivated, namely bidirectionally; for example, artificial treatment such as acute removal of CS or Otx2 (hatched black arrow) resets CP (plastic state) to pre-CP (immature state), and the same applies to post-CP (mature state) that is reset to CP (plastic state).