Neuronal responsiveness to input from the two eyes is established in the visual cortex through an activity-dependent competition during early postnatal life. We previously identified the importance of cortical GABA circuits for critical period (CP) induction, in particular the development of parvalbumin (PV)-positive cells (Hensch, Annu Rev Neurosci. 2004). Maturation of these interneurons and hence critical period timing is specified by the experience-dependent uptake of a homeodomain transcription factor, Otx2 (Sugiyama et al., US SFN Abstr 155.10, 2004). Interestingly, Otx2 transcripts are not detected in visual cortex but are expressed in the retina and LGN. Consistent with a trans-cellular transfer of homeoproteins, intraocular injection of biotinylated-Otx2 is distributed along the visual pathway and specifically transported into PV-cells in visual cortex. Here, to confirm the role of endogenous Otx2, we infused an inhibitory antibody (to block trans-cellular transfer) or penetratin-coupled siRNA (to...