This “small wave”

manipulation strikingly impaired the neural circuit that emerged between the retina and brain during development. This shows that not merely the presence, but the precise spatiotemporal pattern of spontaneous retinal activity instructs neural circuit development. These data are consistent with a body of literature arguing for an important role of activity-dependent competitive processes in mammalian brain development ( Torborg et al., 2005, Chandrasekaran et al., 2005, Mrsic-Flogel et al., 2005, Penn et al., 1998, Cang et al., 2005, Katz and Shatz, 1996, Stryker and Harris, 1986 and Cao et al., 2007) KU-57788 price and demonstrate how even prior to sensory experience, patterned neuronal activity shapes developing brain circuits.

β2(TG) mice have normal retinotopy but profoundly disturbed eye-specific segregation. To our knowledge, this is the first example of a distinction between the activity-dependent requirements for the development of these two visual maps and may reflect a fundamental difference between the process of retinotopic refinement and eye-specific segregation. Eye-specific segregation involves expulsion of “wrong-eye” axons from the domain of the “correct-eye.” In an activity-dependent model, this process requires sufficient correlated intra-eye activity. Retinotopic refinement, in contrast, involves relative spatial correlations within an eye, where the activity of neighboring

Doxorubicin price RGCs is more correlated than that of distant ones. Small retinal waves provide just these local correlations and are therefore adequate for mediating retinotopic refinement in the absence of binocular competition. This interpretation is further supported by our computational TCL model for retinotopy and eye segregation, which is based on axonal competition and a Hebbian, correlation-based synaptic plasticity rule. This model produces both eye-specific segregation and retinotopy for a wide range of parameters only if the waves are sufficiently large, but only retinotopy if the waves are spatially small. In β2(TG) mice, retinotopic refinement is normal everywhere except for the binocular zone of the dLGN and SC. Why? We believe the reason is an interference effect between RGC axons from the two eyes caused by the persistent defects in eye-specific segregation. We demonstrated that the expression of β2-nAChR mRNA is similar in ventral-temporal (binocular projecting) and dorsal-nasal (monocular) retina of β2(TG) mice. Retinal waves are also similar in ventral-temporal and dorsal-nasal retina of WT mice and β2(TG) mice.