Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse

Justin T. Rogers, Lisa Zhao, Justin H. Trotter, Ian Rusiana, Melinda M. Peters, Qingyou Li, Erika Donaldson, Jessica L. Banko, Kathleen E. Keenoy, G. William Rebeck, Hyang Sook Hoe, Gabriella D'Arcangelo, Edwin J. Weeber

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory. Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia. HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition. The present studies test the hypothesis that in vivo elevation of Reelin levels can rescue synaptic and behavioral phenotypes associated with HRM. We demonstrate that a single in vivo injection of Reelin increases GAD67 expression and alters dendritic spine morphology. In parallel we observed enhancement of hippocampal synaptic function and associative learning and memory. Reelin supplementation also increases pre-pulse inhibition. These results suggest that characteristics of HRM, similar to those observed in schizophrenia, are sensitive to Reelin levels and can be modified with Reelin supplementation in male and female adults.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalJournal of Psychopharmacology
Volume27
Issue number4
DOIs
StatePublished - Apr 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Keywords

  • Schizophrenia
  • associative memory
  • glutamic acid decarboxylase 67
  • hippocampus
  • learning and memory
  • long-term potentiation
  • low-density lipoprotein receptors
  • sensorimotor gating

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