162 | Effects of postnatal NMDA receptor ablation in cortical interneurons on social behavior

Cognition, Behavior, and Memory

Author: Juan Martin Uehara | Email: ueharajm@gmail.com

Juan Martín Uehara , Juan Emilio Belforte , Estefanía Pilar Bello

1° Universidad de Buenos Aires – CONICET. Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), Facultad de Medicina, Departamento de Ciencias Fisiológicas. Grupo de Neurociencia de Sistemas. Buenos Aires, Argentina.

Schizophrenia is a chronic neurodevelopmental disorder that includes social withdrawal, blunted affect, and altered discrimination of social stimuli with emotional valence. To date, several attempts have been made to mimic these deficits in animal models, with mixed results. We have previously developed a mutant mouse in which the NR1 subunit of the NMDA receptor is postnatally ablated in GABAergic interneurons of the cortex and hippocampus (InterKO). This mutant has shown preliminary signs of social dysfunction, including mating, nest building, and social memory deficits. The aim of this work was to further characterize the social phenotype of this model related to schizophrenia. To this end, we developed a new behavioral paradigm to determine whether interKO mice can discriminate conspecifics based on their affective states as control mice do. We also devised a second paradigm based on prolonged social interaction to establish whether InterKO mice exhibit a biased preference towards solitary living. Additionally, we conducted resident-intruder and tube tests to study aggression and dominance in mutants. Finally, other tests ruled out possible effects of anxiety and working memory on social behavior. Determining the face validity of the postnatal NR1 knockout mouse is useful for studying the pathophysiology of schizophrenia and for developing new treatments for refractory symptoms.