Effects of Ten_m3 deletion on the visual system: aberrant wiring of ipsilateral retinal projections, an interocular mismatch and visual deficits.


C.A. Leamey1*, S. Merlin1, A. Sawatari1, N. Dharmaratne1, P. Lattouf1, M. Nguyen1, R. Faessler2, & M. Sur3

1Discipline of Physiology, Bosch Institute and School of Medical Sciences, University of Sydney, NSW, 2006 Australia and for Medical Research, Sydney, Australia. 2Dept of Molecular Medicine, Max-Planck Institute for Biochemistry, Martinsreid, Germany. 3Brain and Cognitive Sciences, MIT, Cambridge, MA, 02139 USA.

   

The visual system is characterised by the precise topographic representation of the visual world. This is considered vital for the normal processing of sensory information. We have investigated a role for the transmembrane protein, Ten_m3, in the development of connectivity in the visual pathway. We found that Ten_m3 is expressed in gradients at all levels of the visual pathway, which are consistently highest in regions which represent dorsal visual field. Anterograde tracing from the eye showed that the targeting of ipsilateral retinal axons is aberrant in Ten_m3 knockout (KO) mice. Unlike in wildtype (WT) mice, where ipsilateral terminals are confined to the dorsomedial region of the dorsal lateral geniculate nucleus (dLGN), in Ten_m3 KOs ipsilateral projections are elongated along the dorsomedial to ventrolateral axis of the nucleus. Ipsilateral projections to the superior colliculus (SC) are also more widely distributed than in WTs. Retrograde labeling revealed no change in the number or distribution of ipsilaterally projecting retinal ganglion cells (RGCs). Focal retinal injections showed no change in the topography of contralateral retinal projections, but a major change was observed for the ipsilateral projections. Most notably, 2 distinct terminal zones were present in the ipsilateral dLGN of all KOs examined. Consequently, the projections from the two eyes are not aligned in Ten_m3 KOs. The topography of geniculocortical projections was unchanged, however, suggesting that the interocular mismatch is conveyed to the visual cortex. The impact of this on vision was investigated using behavioural tests. We found that Ten_m3 KOs have pronounced deficits in the performance of visually-mediated behavioural tasks such as the visual–cliff and placement tests. Interestingly, these were reversed by acute monocular inactivation. This suggests that the deficits are a direct consequence of the interocular mismatch, and raises the possibility that the mismatch may mediate a functional suppression. This is being further investigated using c-fos staining and electrophysiology.