Ipsilateral eye axons occupied 10.68 ± 0.44% of the dLGN in controls and 13.03 ±

1.63% in ET33-Cre::VGLUT2flox/flox animals (n = 8 mice for each genotype, p > 0.05 by Student’s t test). Thus, despite having markedly reduced glutamate release throughout the major phase of eye-specific segregation (Figure 2), ipsilateral eye axons were still able to consolidate their normal amount of dLGN territory (Figures 3A and 3D and Figure S3). Spontaneous retinal activity continues beyond P10 and is necessary to maintain eye-specific dLGN territories (Bansal et al., 2000, Chapman, 2000 and Demas et al., 2006). We therefore asked whether normal levels of glutamatergic transmission are necessary to maintain the ipsilateral eye territory in ET33-Cre::VGLUT2flox/flox mice. On P28, contralateral learn more RGC axons were distributed throughout the entire dLGN in ET33-Cre::VGLUT2flox/flox mice (Figures 4A and 4B; n = 7 mice per genotype), similar to the pattern observed in these mice on P10, further indicating that normal levels of glutamate release are crucial for appropriate CNS circuit refinement. However, despite having been at a competitive disadvantage since at least P5, the size of the ipsilateral eye territory

was not diminished in P28 ET33-Cre::VGLUT2flox/flox animals (Figures 4A and 4C). Ipsilateral eye axons consisted of 6.10 ± 0.56% of the dLGN in controls and 7.84 ± 1.73% in ET33-Cre::VGLUT2flox/flox Pictilisib solubility dmso animals

(n = 7 mice for each genotype, p > 0.05 by Mann-Whitney U test). The fact that the patterning of the ipsilateral eye territory in the dLGN was refractory to reductions in glutamate release both during and after the period of eye-specific segregation is surprising as it stands in bold contrast to current models Oxymatrine of activity-dependent retinogeniculate refinement (reviewed in Huberman et al., 2008a) (Figure S4). We found that reducing glutamatergic synaptic currents profoundly altered certain aspects of RGC axon remodeling, whereas other aspects were unaffected. While reduced ipsilateral transmission led to an abnormal persistence of competing contralateral eye axons in the ipsilateral eye territory (Figures 3A and 3D), it did not prevent ipsilateral eye axons from (1) targeting to the appropriate region of the dLGN (Figure 3A), (2) refining into a normally sized termination zone (Figures 3A and 3E), and (3) maintaining that territory into the late postnatal period (Figures 4A and 4C). The ability of the release-deficient axons to consolidate and maintain their normal amount of target territory in the face of more active competing axons is surprising in light of previous studies (Chapman, 2000, Demas et al., 2006, Penn et al., 1998 and Stellwagen and Shatz, 2002).