Early Postnatally Induced Conditional Reelin Deficiency Causes Malformations of Hippocampal Neurons

The extracellular matrix protein reelin is well known for orchestrating radial migration of cortical neurons during embryonic cortical development. While in the <i>reeler</i> mutant mouse, lacking reelin expression, radially migrating neurons are malpositioned and display dendritic malformations, no such deficits were found after conditionally induced reelin deficiency (Reln^cKO) in the hippocampus of mice aged two months. Here, we addressed the question whether or not Reln^cKO, when induced early after birth, might cause malformations of hippocampal neurons. For instance, we could recently show dendritic hypertrophy of somatosensory and entorhinal cortex neurons after early induced Reln^cKO. In the present study, reelin deficiency in Reln^cKO mice was induced immediately after birth, and the analysis of reconstructed Golgi-stained hippocampal neurons from these mice, when aged 4 weeks, revealed morphological malformations. Dentate granule cells were the most affected from all analyzed hippocampal neuronal cell types. Thus, Reln^cKO granule cells had a significantly smaller soma size and displayed atrophy of proximal dendritic segments when compared to wild type (wt). Malformations of interneurons were only subtle and cell type specific; thus, multipolar but not bitufted interneurons developed proximal dendritic hypertrophy. Also, the dendrite morphology of CA2- and CA3-pyramidal cells was affected, while we did not detect morphological changes of CA1-pyramidal cell dendrites. In summary, our results show that early postnatal Reln^cKO causes morphological malformations of hippocampal neurons, in particular of dentate granule cells. Taken together with our previous findings, we conclude that not only specific types of entorhinal- and neocortical neurons, but also types of hippocampal neurons are at risk of developing malformations if reelin expression is reduced during a critical early postnatal period.