In vivo imaging demonstrates dendritic spine stabilization by SynCAM 1

Sci Rep. 2016 Apr 7:6:24241. doi: 10.1038/srep24241.

Abstract

Formation and stability of synapses are required for proper brain function. While it is well established that synaptic adhesion molecules are important regulators of synapse formation, their specific role during different phases of synapse development remains unclear. To investigate the function of the synaptic cell adhesion molecule SynCAM 1 in the formation, stability, and maintenance of spines we used 2-photon in vivo imaging to follow individual spines over a long period of time. In SynCAM 1 knockout mice the survival rate of existing spines was reduced and fewer filopodia-like structures were converted into stable spines. SynCAM 1(flag) overexpression resulted in more stable spines and fewer filopodia-like structures. When SynCAM 1(flag) overexpression is turned on the spine density rapidly increases within a few days. Interestingly, the spine density stayed at an elevated level when SynCAM 1(flag) overexpression was turned off. Our data indicate that the SynCAM 1 induced altered spine density is not caused by the formation of newly emerging protrusions, instead SynCAM 1 stabilizes nascent synaptic contacts which promotes their maturation. Concomitant with the synaptic stabilization, SynCAM 1 generally prolongs the lifetime of spines. In summary, we demonstrate that SynCAM 1 is a key regulator of spine stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Doxycycline / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunoblotting
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton / methods*
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Synapses / drug effects
  • Synapses / metabolism*
  • Time Factors

Substances

  • Cadm1 protein, mouse
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Green Fluorescent Proteins
  • Doxycycline