Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission

Neuropsychopharmacology. 2016 Feb;41(3):802-10. doi: 10.1038/npp.2015.206. Epub 2015 Jul 14.


Calsyntenin-2 has an evolutionarily conserved role in cognition. In a human genome-wide screen, the CLSTN2 locus was associated with verbal episodic memory, and expression of human calsyntenin-2 rescues the associative learning defect in orthologous Caenorhabditis elegans mutants. Other calsyntenins promote synapse development, calsyntenin-1 selectively of excitatory synapses and calsyntenin-3 of excitatory and inhibitory synapses. We found that targeted deletion of calsyntenin-2 in mice results in a selective reduction in functional inhibitory synapses. Reduced inhibitory transmission was associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex. Clstn2(-/-) mice showed normal behavior in elevated plus maze, forced swim test, and novel object recognition assays. However, Clstn2(-/-) mice were hyperactive in the open field and showed deficits in spatial learning and memory in the Morris water maze and Barnes maze. These results confirm a function for calsyntenin-2 in cognitive performance and indicate an underlying mechanism that involves parvalbumin interneurons and aberrant inhibitory transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Calcium-Binding Proteins / deficiency*
  • Calcium-Binding Proteins / genetics
  • Cognition Disorders / metabolism*
  • Exploratory Behavior / physiology
  • Female
  • Fluorescent Antibody Technique
  • Interneurons / metabolism*
  • Male
  • Maze Learning / physiology
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology
  • Neural Inhibition / physiology
  • Parvalbumins / metabolism
  • Recognition, Psychology / physiology
  • Spatial Memory / physiology
  • Synaptic Transmission / physiology*
  • Tissue Culture Techniques
  • gamma-Aminobutyric Acid / metabolism*


  • Calcium-Binding Proteins
  • Membrane Proteins
  • Parvalbumins
  • calsyntenin-2, mouse
  • gamma-Aminobutyric Acid