Reelin regulates the development and synaptogenesis of the layer- specific entorhino-hippocampal connections

Víctor Borrell, José A. Del Río, Soledad Alcántara, Michèle Derer, Albert Martínez, Gabriella D'Arcangelo, Kazunori Nakajima, Katsuhiko Mikoshiba, Paul Derer, Tom Curran, Eduardo Soriano

Research output: Contribution to journalArticlepeer-review

170 Citations (Scopus)


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 cocultures 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.

Original languageEnglish
Pages (from-to)1345-1358
Number of pages14
JournalJournal of Neuroscience
Issue number4
Publication statusPublished - 1999 Feb 15
Externally publishedYes


  • Cajal-Retzius cells
  • Hippocampus
  • Neuronal connections
  • Reeler mutant mouse
  • Reelin
  • Synaptic specificity

ASJC Scopus subject areas

  • General Neuroscience


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