In this study, we determined the contribution of juvenile neurogenesis to the performance of mice on a remote memory for temporally based association task and in a novelty based spatial pattern separation task. This was accomplished by mating homozygous DNMT1‐loxP mice with heterozygous GFAP‐Cre mice and comparing Cre+ (no postnatal neurogenesis) to Cre− (wild type) littermate offspring. The results indicate that Cre+ mice are impaired relative to Cre− mice in the remote memory for a temporal based association task and in a novelty based spatial pattern separation task. These results support the temporal integration model of Aimone et al., [(2006) Nat Neurosci 9:723–727] and provide further support for an important role for postnatally born neurons in spatial pattern separation. In contrast, Cre+ mice are not impaired relative to Cre− mice in an object‐context recognition task and a spatial location recognition task. These latter data suggest that postnatally derived neurons in the dentate gyrus (DG) do not support all spatial and object recognition functions of the DG. © 2014 Wiley Periodicals, Inc.

Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA). In Lrat -/mouse model, mislocalized medium (M)-wavelength sensitive opsin was degraded whereas mislocalized short (S)-wavelength sensitive opsin accumulated before the onset of cone degeneration. The mechanism for the foveal medium (M)/long (L)-wavelength-sensitive cone degeneration in LCA is unknown. By crossing Lrat -/mice with a proteasome reporter mouse line, we showed that M-opsin enriched dorsal cones in Lrat -/mice exhibit proteasome stress due to the degradation of large amounts of Mopsin. Deletion of M-opsin relieves the proteasome stress and completely prevents "M cone" degeneration in Lrat -/-Opn1sw -/mice (a pure "M cone" LCA model, Opn1sw -/encoding Sopsin) for at least 12 months. Our results suggest that M-opsin degradation associated proteasome stress plays a major role in "M cone" degeneration in Lrat -/model. This finding may represent a general mechanism for "M cone" degeneration for multiple forms of cone degeneration due to M-opsin mislocalization and degradation. Our results have important implications for the current gene therapy strategy for LCA that emphasizes the need for a combinatorial therapy to both improve vision and slow photoreceptor degeneration.

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