, 1998 and Crair et al., 2001). An important caveat of our experimental manipulation is that it did not eliminate glutamate release completely. The present study, therefore, cannot determine if glutamate Depsipeptide release is necessary for axon territory consolidation and maintenance. In addition, it is not presently possible to measure the effects of VGLUT2 reduction on RGC-dLGN transmission patterns in vivo; therefore, a full assessment of the synaptic defects present in

ET33-Cre::VGLUT2flox/flox mice during retinal waves remains to be determined. As it stands, the residual glutamate release observed in ET33-Cre::VGLUT2flox/flox mice at P5 may be sufficient to stabilize and refine their ipsilateral RGC axons, whereas the mechanism that eliminates competing axons may be more sensitive to alterations in glutamate release. Why would ipsilateral axons refine normally with diminished VGLUT2 (Figure 3), Ixazomib research buy whereas monocular activity perturbations lead to a reduced ipsilateral eye territory (Koch

and Ullian, 2010 and Penn et al., 1998)? The differences in those outcomes may reflect differences between the experimental manipulations in the studies. While VGLUT2 reduction weakened retinogeniculate transmission during eye-specific segregation (Figure 2), intraocular epibatidine treatment altered RGC spiking patterns (Penn et al., 1998 and Sun et al., 2008), which in theory should cause abnormal transmission patterns at RGC-dLGN synapses. Abnormal

patterns of synaptic activity may lead to a punishment signal that causes axons to be lost, whereas axons with dramatically weakened (or abolished) synaptic currents may fail to elicit or respond to such a signal. Another potential explanation is that in addition to evoking Oxalosuccinic acid glutamate release from RGC axons, retinal waves cause calcium influxes in RGCs. Therefore, manipulations that alter spontaneous retinal activity patterns may exert broader effects on RGC axons than does VGlut2 reduction. A third possibility is that RGC axons may release factors other than glutamate to control the consolidation of their target territory and those factors may be differentially impacted by epibatidine versus VGLUT2 reduction. For instance, RGCs express the vesicular monoamine transporter 2 (VMAT2) during development and the very promoter used to drive Cre expression in ipsilateral RGCs—SERT—is specifically expressed by ipsilateral RGCs during development (Upton et al., 1999 and García-Frigola and Herrera, 2010). Indeed, eye-specific layers fail to form in animals lacking monoamine oxidase or SERT (Upton et al., 1999).