RT Journal Article SR Electronic T1 Reelin Regulates the Development and Synaptogenesis of the Layer-Specific Entorhino-Hippocampal Connections JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1345 OP 1358 DO 10.1523/JNEUROSCI.19-04-01345.1999 VO 19 IS 4 A1 Vı́ctor Borrell A1 José A. Del Rı́o A1 Soledad Alcántara A1 Michèle Derer A1 Albert Martı́nez A1 Gabriella D’Arcangelo A1 Kazunori Nakajima A1 Katsuhiko Mikoshiba A1 Paul Derer A1 Tom Curran A1 Eduardo Soriano YR 1999 UL http://www.jneurosci.org/content/19/4/1345.abstract AB Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.