The mechanisms which coordinate the generation of visuotopically aligned eye-specific inputs, such that a cohesive map of visual space is generated in the primary visual cortex (V1), have been the subject of intense scrutiny over recent decades. Recent work by our group has identified a developmentally expressed protein, Ten-m3, that plays a unique and important role in the generation of visuotopically aligned eye-specific projections to subcortical visual centres in mice. In the absence of Ten-m3, ipsilateral, but not contralateral inputs are dramatically mistargeted in the dorsal lateral geniculate nucleus (dLGN). Behavioural testing revealed a marked visual deficit which, remarkably, was reversed by acute monocular inactivation. This led us to hypothesise that altered interocular interactions may act to suppress vision in Ten-m3 knockouts (KOs). The aim of this study is to determine how the subcortical axon guidance errors impact the anatomical and functional organisation of primary visual cortex (V1), and thus whether they may underlie the remarkable behavioural phenotype. Transneuronal tracing with 3H-proline revealed that ipsilateral inputs map to medial, normally monocular V1 in Ten-m3 KOs, rather than remaining confined to the lateral region as in wildtype (WT) mice. Immunoreactivity for c-fos, a marker of activity, shows that the ipsilateral inputs are able to drive activity in medial V1 under monocular conditions in KOs. This contrasts with WTs where activity is confined to lateral V1. Interestingly, the ipsilaterally-driven cortical neurons are clustered in patches across V1 in KOs suggesting that there may be some functional segregation of eye-specific inputs. Optical imaging of intrinsic signals confirms the presence of ipsilaterally driven patches in medial V1 and further suggests that contralateral topography is unaltered in Ten_m3 KOs. In vivo single-unit electrophysiological recording supports this and further shows that individual cortical neurons receive topographically appropriate inputs from the contralateral eye and topographically inappropriate inputs through the ipsilateral eye. The demonstration that spatially divergent inputs from the two eyes converge on single cortical neurons suggests that the altered subcortical mapping has the capacity to cause profound changes in interocular interactions which may thus underlie the reversible visual deficit in Ten-m3 KOs.

Society for Neuroscience Abstract, 2009.