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H. Xu, Y. S. Mineur, H. Chen, M. R. Picciotto, N. Tian, D. Zenisek, M. C. Crair; Conditional Expression of β2-Containing Nicotinic Acetylcholine Receptor in Retina Rescues Retinocollicular Map Refinement. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3866.
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Synchronous spontaneous retinal activity (retinal ‘wave’) during the first week after birth instructs retinotopic map refinement in the superior colliculus (SC). The absence of nicotinic acetylcholine receptor (nAChR) β2 subunits in constitutive knockout (KO) mice eliminates early retinal waves and results in abnormally large retinal ganglion cell (RGC) axonal termination zones in the SC. Normally, nAChR β2 subunits are expressed in both the retina and SC. To exclude the possibility that cholinergic expression by cells in the SC plays a role in map refinement, we examined mice with targeted expression of the β2 subunit in the retina, but not the SC. We quantified the SC axon termination zone of a small group of neighboring RGCs in mice with targeted expression of the β2 subunit in the retina, in comparison with wild type (WT) mice and β2 subunit KO mice.
Spontaneous retinal activity was measured in these three groups of mice using a multi-electrode array system at P4. The size of RGC axonal termination zones in the SC was determined by focal intraretinal injections of DiI at P6 and the target zone of RGCs in the SC was imaged at P8.
Consistent with previous reports, the axonal target zone of RGCs at P8 in the SC was already confined to a small area in WT mice, and RGC firing activity was highly synchronized, with spike bursts driven by cholinergic synaptic transmission during the first postnatal week. However, target zone refinement was disrupted in the global β2 KO mice, and spontaneous retinal activity and the synchronized firing pattern of RGCs was largely lost. Re-expression of β2 subunit-containing nAChR in the retina partially restored retinal wave activity at P4 and completely rescued retinocollicular map refinement at P8.
The disruption of retinocollicular map refinement observed in β2 KO mice results from the loss of retinal β2, presumably because of the absence of retinal waves. nAChR β2 subunit expression by cells in the SC is not necessary for retinocollicular map refinement.
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