Poster Sessions

Neu-31

Juan Belforte

J. E. Belforte, V. Zsiros, E. R. Sklar, Y. Li, G. Kunos, K. Nakazawa

Forebrain Gabaergic Interneurons-Restricted NMDA Receptor Ablation Before Adolescence Results In Psychiatric-Like Behavior.

Converging clinical evidence suggests that altered GABAergic function may underlie the pathophysiology of psychiatric disorders.GABAergic dysfunction in these disorders may result from hypofunction of NMDA-type glutamate receptors (NRs) in cortical interneurons. To explore this hypothesis we genetically ablated the NMDA receptor subunit 1 (NR1) predominantly in forebrain GABAergic cells, using a newly generated transgenic Cre line, before adolescence. Behavior analysis of mutant mice revealed increased levels of anxiety-like behaviors without any abnormal motor function. Significant hyperlocomotion was observed only during the first several minutes of exploration in new open fields. Mutants also displayed decreased prepulse inhibition and spontaneous alternation in Y maze decreased to chance levels suggesting a working memory deficit. Moreover, nest construction, breeding, mating, and social recognition were impaired in mutants. Social isolation-induced stress precipitated mutant phenotypes. In addition, when NR1 was genetically ablated in the same population of cells starting at 8-weeks-old using a different floxed-NR1 strain, we observed no such behavioral phenotypes, suggesting that preadolescent NR1 ablation is critical for development of the psychiatric-like behavior. Taken together, the present results suggest that loss of NR function in cortical and hippocampal GABAergic cells during postnatal development leads to psychiatric-like behavior, which can be precipitated by social stress.