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

PRETELL ANNAN, CARLOS A; PAFUNDO, DIEGO ESTEBAN; BELFORTE, J.E.

Congreso; Reunion Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Schizophrenia (SZ) is a chronic mental disorder usually emerging during adolescence and early adulthood thatencompasses disruptions in various symptomatic domains, sometimes leading to profound disability. Althoughits etiology is not yet thoroughly understood, cortical parvalbumin expressing interneurons (PVs) have beenpathophysiologically 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-likebehavioral phenotype, although its developmental trajectory had not been fully described. Therefore, we aimedto characterize the time course of behavioral alterations, with a special emphasis in presymptomatic stages. Toaddress this, we evaluated mice behavior throughout development, from PND 25 to 20 weeks of age, by meansof an open field (OF), a spontaneous alternation Y-maze (YM), nesting and marble burying (MB). Here weconfirmed previous findings for OF, YM and nesting, with hyperlocomotion and memory deficit emerging atadulthood. We also found this altered behavior in MB. Remarkably, we found a transient deficit in YM occurringbefore 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 inadulthood, some traits may be present at early stages as preclinical entities.