Impaired clustered protocadherin-alpha leads to aggregated retinogeniculate terminals and impaired visual acuity in mice

摘要

Clustered protocadherins (cPcdhs) comprising cPcdh-, -, and -, encode a large family of cadherin-like cell-adhesion molecules specific to neurons. Impairment of cPcdh- results in abnormal neuronal projection patterns in specific brain areas. To elucidate the role of cPcdh- in retinogeniculate projections, we investigated the morphological patterns of retinogeniculate terminals in the lateral geniculate (LG) nucleus of mice with impaired cPcdh-. We found huge aggregated retinogeniculate terminals in the dorsal LG nucleus, whereas no such aggregated terminals derived from the retina were observed in the olivary pretectal nucleus and the ventral LG nucleus. These aggregated terminals appeared between P10 and P14, just before eye opening and at the beginning of the refinement stage of the retinogeniculate projections. Reduced visual acuity was observed in adult mice with impaired cPcdh-, whereas the orientation selectivity and direction selectivity of neurons in the primary visual cortex were apparently normal. These findings suggest that cPcdh- is required for adequate spacing of retinogeniculate projections, which may be essential for normal development of visual acuity.