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 ␣7 homomeric nAChRs on visual function was investigated using mutant mice lacking the ␣7 nicotinic receptor subunit. METHODS. The spatial resolution limit was measured in ␣7 knockout (␣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 ␣7 KO mice and, concordantly, there was a reduction of the cortical spatial resolution limit measured by VEPs. However, the PERG was normal in ␣7 KO mice, compared with control mice. The use of fluorescently tagged cholera toxin showed that projections from the retina segregate normally in ␣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 ␣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 N icotinic receptors (nAChRs) represent a heterogeneous family of ion channels that are differently expressed in the nervous system. There are 12 subunit genes that derive from a common ancestral gene: 9 ␣ subunits (␣2 to ␣10) and 4  subunits (2 to 4). Neuronal nAChRs fall into two main classes: homomeric or heteromeric ␣-bungarotoxin (␣Bgtx)-sensitive receptors consisting of ␣7, ␣8, or ␣7-␣8 and/or ␣10 subunits and ␣Bgtx-insensitive heteromeric receptors consisting of ␣2-␣6 and 2-4 subunits. Nicotinic AChRs are permeable to Na ϩ , K ϩ , and Ca 2ϩ ions, and their cation permeability is influenced by their subunit composition. The ␣7 subunit that forms native pentameric homomeric receptors is highly expressed in the hippocampus, hypothalamus, and neocortex of rodents. 1 Alpha-7 knockout (KO) mice, which are characterized by the loss of ␣Bgtx receptors and the lack of nicotineevoked fast desensitizing currents in neurons, 2 are viable with apparently normal brain anatomy. In terms of behavior, the performance of ␣7 KO mice in the classic Morris water maze test, the Pavlovian conditioned fear test and the prepulse inhibition paradigm are similar to those of wild-type (WT) mice, which suggests that the absence of ␣7 nAChRs has little impact on normal, baseline behavioral responses. 3 Moreover, ␣7 KO mice show a reduced anxietyrelated response, 3 whereas only mice lacking both the ␣7 and the 2 nAChR subunits show impaired learning and memory in a passive avoidance test, and enhanced motor activity on the rota rod. 6 Although ␣7 KO mice are widely used in behavioral studies, no attempt has been made to characterize their visual function. The ␣7 subunit is widely expressed in the visual system, particularly in the retina and retinal input recipient regions such as the dorsolateral geniculate nucleus (dLGN), the superior colliculus, and the visual cortex
