Preweaning sensorimotor deficits and adolescent hypersociability in Grin1 knockdown mice.

Abstract

Mice with knockdown of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit, encoded by the gene Grin1, have been investigated as a model for the intrinsic NMDA hypofunction hypothesized for schizophrenia. Previous work has shown that adult Grin1 mutant mice have overt deficits in habituation and sensorimotor gating, exaggerated reactivity to environmental stimuli, reduced social approach, and other alterations that reflect behavioral manifestations of schizophrenia. In humans, the emergence of overt symptoms of the disorder typically occurs in adolescence or early adulthood, suggesting a role for aberrant maturation of NMDA receptor signaling in symptom onset. The following study evaluated Grin1 mutant mice for abnormal behavioral phenotypes during the preweaning, adolescent, and adult periods. Measures included open field activity, prepulse inhibition of acoustic startle responses, and social preference in a three-chamber choice task. Mice from the C57BL/6J inbred strain, one of the parental strains for the Grin1 line, were also tested. The results showed that developmental reduction of NMDA receptor function led to significant alterations in behavior during the second and third weeks of life, including exaggerated startle responses and sensorimotor gating deficits on postnatal day 13, and pronounced hypersociability in adolescence. Male Grin1 mutant mice were more susceptible than female mice to the detrimental effects of decreased NMDA signaling. Overall, these findings provide evidence that reduced Grin1 function leads to abnormal phenotypes in the preweaning period, and that deficient NMDA signaling can lead to both overt hypersociability or marked asociality, dependent upon sex and age.

• Authors: Sheryl S Moy, Viktoriya D Nikolova, Natallia V Riddick, Lorinda K Baker, Beverly H Koller
• Journal: Developmental neuroscience (Dev Neurosci) Vol. 34 Issue 2-3 Pg. 159-73 ( 2012) ISSN: 1421-9859 [Electronic] Switzerland
• PMID: 22571986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• NR1 NMDA receptor
• Receptors, N-Methyl-D-Aspartate

Topics

• Age Factors
• Animals
• Behavior, Animal (physiology)
• Choice Behavior (physiology)
• Disease Models, Animal
• Female
• Male
• Mice
• Mice, Transgenic
• Motor Activity (genetics)
• Receptors, N-Methyl-D-Aspartate (genetics, metabolism)
• Reflex, Startle (genetics)
• Schizophrenia (genetics, physiopathology)
• Sensory Gating (genetics)
• Sex Factors
• Social Behavior