Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long-term potentiation

J Neurosci. 2010 Mar 31;30(13):4636-49. doi: 10.1523/JNEUROSCI.5284-09.2010.

Abstract

Reelin, an extracellular protein essential for neural migration and lamination, is also expressed in the adult brain. To unravel the function of this protein in the adult forebrain, we generated transgenic mice that overexpress Reelin under the control of the CaMKIIalpha promoter. Overexpression of Reelin increased adult neurogenesis and impaired the migration and positioning of adult-generated neurons. In the hippocampus, the overexpression of Reelin resulted in an increase in synaptic contacts and hypertrophy of dendritic spines. Induction of long-term potentiation (LTP) in alert-behaving mice showed that Reelin overexpression evokes a dramatic increase in LTP responses. Hippocampal field EPSP during a classical conditioning paradigm was also increased in these mice. Our results indicate that Reelin levels in the adult brain regulate neurogenesis and migration, as well as the structural and functional properties of synapses. These observations suggest that Reelin controls developmental processes that remain active in the adult brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cell Movement
  • Conditioning, Classical
  • Dendritic Spines / ultrastructure*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Long-Term Potentiation*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurogenesis
  • Neurons / physiology
  • Neurons / ultrastructure
  • Promoter Regions, Genetic
  • Prosencephalon / growth & development
  • Prosencephalon / metabolism*
  • Prosencephalon / ultrastructure
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Synapses / physiology
  • Synapses / ultrastructure

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Serine Endopeptidases
  • reelin protein