Region-specific morphological deficits of hippocampal neurons after postnatally induced reelin deficiency

The extracellular matrix glycoprotein reelin is best known for orchestrating migration and positioning of cortical neurons during embryonic development. The reeler mutant mouse, lacking reelin expression, displays severe migration defects and aberrant dendritic development of cortical neurons. Less is known about the consequences of postnatally induced reelin deficiency in conditional reelin knockout (reln cko) mice. Postnatally induced reln cko was shown to entail functional deficits of neuronal communication, while morphological deficits of neurons have not been reported so far. Here, we investigated whether tamoxifen induced reln cko immediately after birth causes morphological defects of hippocampal neurons in adult mice. Mice were sacrificed four weeks after tamoxifen induced reln cko, brains were fixed and rapid golgi staining was performed. Neurons were reconstructed and their morphology was analyzed using neurolucida software. Our results show that from all hippocampal neuronal cell types, dentate granule cells were most affected by postnatal reln cko, with reduced soma size, atrophic dendritic trees and curved proximal dendritic segments. Interestingly, the morphology of CA1 pyramidal cells remained unchanged, while CA2 pyramidal neurons displayed a reduced soma size. Both CA2- and CA3-pyramidal cells displayed signs of dendritic atrophy and changes in apical dendrite orientation. Non-bipolar interneurons did not change, while bipolar interneurons showed curved proximal dendritic segments and hypertrophic dendritic trees. In sum, for the first time we report here on differential morphological deficits of hippocampal neurons after postnatally induced reelin deficiency.