Failure to Maintain Eye-Specific Segregation in nob, a Mutant with Abnormally Patterned Retinal Activity

Abstract

Axon terminals from the two eyes initially overlap in the dorsal-lateral geniculate nucleus (dLGN) but subsequently refine to occupy nonoverlapping territories. Retinal activity is required to establish and maintain this segregation. We show that despite the presence of retinal activity, segregated projections desegregate when the structure of activity is altered. Early in development, spontaneous retinal activity in the no b-wave (nob) mouse is indistinguishable from that of wild-type mice, and eye-specific segregation proceeds normally. But, around eye-opening, spontaneous and visually evoked activity in nob retinas become abnormal, coincident with a failure to preserve precise eye-specific territories. Dark-rearing studies suggest that altered visual experience is not responsible. Transgenic rescue of the mutated protein (nyctalopin) within nob retinal interneurons, without rescuing expression in either retinal projection neurons or their postsynaptic targets in the dLGN, restores spontaneous retinal activity patterns and prevents desegregation. Thus, normally structured spontaneous retinal activity stabilizes newly refined retinogeniculate circuitry.

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

“…The reason for these difference is unclear, but may indicate abnormalities in postreceptoral Off pathway activity of Nob mice. In fact, in extracellular recordings from Off ganglion cells in Nob mice, activity has been observed to be abnormal (Demas et al, 2006;Gregg et al, 2007). Importantly however, both in Nob mice and Control mice injected with APB the positive intrusion was completely removed (see Figs.…”

“…As in humans with CSNB-1, the Nob ERG lacks a b-wave [as indicated by the name, no b-wave (Nob)], although the corneal negative a-wave looks normal (Candille et al, 1999;Pardue et al, 1998). Expression of Nyx has been found to be strong in mouse retina INL, using in situ hybridization , and transgenic rescue of the mutated nyctalopin can restore function (Demas et al, 2006;Gregg et al, 2007). The Nob mouse is now sometimes termed the Nob1 mouse because other no b-wave mice, numbering up to Nob4, to date, with different mutations have been characterized.…”

“…It also has been shown that the absence of nyctalopin in Nob mice does not disrupt the expression pattern of other proteins required for synaptic transmission . Given the relatively normal appearance of the retina, the postreceptoral components of the ERG originating from hyperpolarizing bipolar cells and 3 rd order neurons should still be present in the response, although recent ganglion cell recordings show abnormalities in inner retinal activity beyond those expected for a defect localized to On bipolar cells (Demas et al, 2006;Gregg et al, 2007).…”

Ephrin-As and Patterned Retinal Activity Act Together in the Development of Topographic Maps in the Primary Visual System

“…A strong candidate that may facilitate this role is the ␤2-independent retinal waves that occur during the second and third postnatal weeks. Mice with defects in these ACh-independent retinal waves fail to maintain normal segregation of eye-specific layers in the dLGN (Demas et al, 2006); however, the role of these waves in topography has not been addressed. It remains possible that these waves, or perhaps visually driven activity, can provide positional information used to maintain or establish retinotopy in the dLGN.…”

Functional and structural impact of the loss of the leucine-rich repeat protein LRIT1 in the mouse retina.

“…Retinal oscillations also occur in the Nyx nob mouse retinas (63,126). To examine this, we used fast Fourier transform (FFT) in a power spectral density to determine if there was rhythmicity to the spontaneous activity.…”