Causal links between excitatory synaptic dysfunction at cortico-striatal synapses and OCD-relevant behaviors have also been drawn from rodent studies. Mice with constitutive knockout of Sapap3 (also known as Dlgap3), a post-synaptic density protein enriched at excitatory cortico-striatal synapses, or Slitrk5, a post-synaptic transmembrane protein found in excitatory synapses, display compulsive grooming phenotypes and cortical (Slitrk5-KO) and striatal (Sapap3-KO) hyperactivity that can be rescued with chronic fluoxetine (the first-line pharmacotherapy for OCD) treatment33–35. Furthermore, these models have altered expression of glutamate receptor transcripts within the striatum33, suggesting that removal of critical post-synaptic proteins affects both the structure and function of cortico-striatal synapses and may contribute to compulsive behavior.
