Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Dab1 is required for synaptic plasticity and associative learning

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Trotter, J.
  • Lee, G. H.
  • Kazdoba, T. M.
  • Crowell, B.
  • Domogauer, J.
  • Mahoney, H. M.
  • Franco, S. J.
  • Mueller, Ulrich
  • Weeber, E. J.
  • D'Arcangelo, G.

publication date

  • September 2013

journal

  • Journal of Neuroscience  Journal

abstract

  • Disabled-1 (Dab1) is an adaptor protein that is an obligate effector of the Reelin signaling pathway, and is critical for neuronal migration and dendrite outgrowth during development. Components of the Reelin pathway are highly expressed during development, but also continue to be expressed in the adult brain. Here we investigated in detail the expression pattern of Dab1 in the postnatal and adult forebrain, and determined that it is expressed in excitatory as well as inhibitory neurons. Dab1 was found to be localized in different cellular compartments, including the soma, dendrites, presynaptic and postsynaptic structures. Mice that are deficient in Dab1, Reelin, or the Reelin receptors ApoER2 and VLDLR exhibit severely perturbed brain cytoarchitecture, limiting the utility of these mice for investigating the role of this signaling pathway in the adult brain. In this study, we developed an adult forebrain-specific and excitatory neuron-specific conditional knock-out mouse line, and demonstrated that Dab1 is a critical regulator of synaptic function and hippocampal-dependent associative and spatial learning. These dramatic abnormalities were accompanied by a reduction in dendritic spine size, and defects in basal and plasticity-induced Akt and ERK1/2 signaling. Deletion of Dab1 led to no obvious changes in neuronal positioning, dendrite morphology, spine density, or synaptic composition. Collectively, these data conclusively demonstrate an important role for Reelin-Dab1 signaling in the adult forebrain, and underscore the importance of this pathway in learning and memory.

subject areas

  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Dendrites
  • Extracellular Matrix Proteins
  • Hippocampus
  • LDL-Receptor Related Proteins
  • Learning
  • MAP Kinase Signaling System
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Prosencephalon
  • Proto-Oncogene Proteins c-akt
  • Receptors, LDL
  • Serine Endopeptidases
  • Synapses
scroll to property group menus

Identity

PubMed Central ID

  • PMC3782631

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.2010-13.2013

PubMed ID

  • 24068831
scroll to property group menus

Additional Document Info

start page

  • 15652

end page

  • 15668

volume

  • 33

issue

  • 39

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support