Otx2-PNN Interaction to Regulate Cortical Plasticity

Abstract

The ability of the environment to shape cortical function is at its highest during critical periods of postnatal development. In the visual cortex, critical period onset is triggered by the maturation of parvalbumin inhibitory interneurons, which gradually become surrounded by a specialized glycosaminoglycan-rich extracellular matrix: the perineuronal nets. Among the identified factors regulating cortical plasticity in the visual cortex, extracortical homeoprotein Otx2 is transferred specifically into parvalbumin interneurons and this transfer regulates both the onset and the closure of the critical period of plasticity for binocular vision. Here, we review the interaction between the complex sugars of the perineuronal nets and homeoprotein Otx2 and how this interaction regulates cortical plasticity during critical period and in adulthood.

Figure 1

Otx2-PNN feedback loop for critical period plasticity. At critical period (CP) onset, sensory activity induces initial formation of the perineuronal nets (PNNs), allowing the internalization of extracortical Otx2 by PV-cells. During CP, the increasing PV-cell Otx2 content enhances PNN assembly. In turn, PNNs ensure the specific accumulation of Otx2 in the PV-cells. In the adult, the constant transfer of Otx2 into the PV-cells, due to the positive feedback loop between the homeoprotein and the PNNs, maintains a mature, consolidated, nonplastic state. Indeed, interfering with Otx2-PNN interaction in the adult (by injecting ChABC to remove PNNs or by infusing the GAG-binding domain of Otx2 (RK-peptide) or a CS-E analogue to block Otx2) reopens a window of plasticity in the visual cortex.