Behavioral alterations in an NMDA receptor knockout mouse model of schizophrenia mainly emerge after adolescence

BELFORTE, JUAN E.; PAFUNDO, DIEGO E.; PRETELL ANNAN, CARLOS A.

Villa Carlos Paz, Cordoba

Congreso; XXXIV Reunion anual SAN; 2019

Sociedad argentina de investigacion en neurociencias

Schizophrenia (SZ) is a chronic mental disorder usually emerging during adolescence and early adulthood that encompasses disruptions in various symptomatic domains, sometimes leading to profound disability. Although its etiology is not yet thoroughly understood, cortical parvalbumin expressing interneurons (PVs) have been pathophysiologically implicated. Also, it is known that PVs normally complete their maturation around SZ onset. We have shown that early postnatal ablation of NMDA receptors in cortical PVs results in an adult SZ-like behavioral phenotype, although its developmental trajectory had not been fully described. Therefore, we aimed to characterize the time course of behavioral alterations, with a special emphasis in presymptomatic stages. To address this, we evaluated mice behavior throughout development, from PND 25 to 20 weeks of age, by means of an open field (OF), a spontaneous alternation Y-maze (YM), nesting and marble burying (MB). Here we confirmed previous findings for OF, YM and nesting, with hyperlocomotion and memory deficit emerging at adulthood. We also found this altered behavior in MB. Remarkably, we found a transient deficit in YM occurring before adolescence. Also, differences were seen between males and females for the first time. In conclusion, while the majority of SZ-related phenotypes induced by early postnatal NMDA receptor ablation emerge in adulthood, some traits may be present at early stages as preclinical entities.