Visual Acuity Is Reduced in Alpha 7 Nicotinic Receptor Knockout Mice

PURPOSE. Nicotinic receptors (nAChRs) are part of a heterogeneous family of pentameric ligand-gated ion channels that are widely expressed in the visual system. The impact of alpha 7 homomeric nAChRs on visual function was investigated using mutant mice lacking the alpha 7 nicotinic receptor subunit. METHODS. The spatial resolution limit was measured in alpha 7 knockout (alpha 7 KO) and age-matched control mice using three independent methods: an operant behavioral visual task (Prusky maze), cortical visual evoked potentials (VEPs), and the pattern electroretinogram (PERG) evoked by alternating gratings of different spatial frequencies and contrasts. RESULTS. Visual acuity measured by means of the visual water maze task was significantly decreased in the alpha 7 KO mice and, concordantly, there was a reduction of the cortical spatial resolution limit measured by VEPs. However, the PERG was normal in alpha 7 KO mice, compared with control mice. The use of fluorescently tagged cholera toxin showed that projections from the retina segregate normally in alpha 7 KO mice and, in line with this, the visual cortical responses elicited by stimulating either eye were normally balanced in both visual cortices and showed no retinotopic anomalies. CONCLUSIONS. These findings indicate that the absence of the alpha 7 nicotinic subunit reduces visual acuity. Because the cortical output has an abnormal spatial resolution but retinal output is preserved, it can be concluded that the low visual acuity was due to a deficit specifically present in the visual cortex. (Invest Ophthalmol Vis Sci. 2012;53:1211-1218) DOI:10.1167/iovs.11-8007