Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene.

Abstract

GABAergic interneuron loss, maturational delay or imbalance of glutamatergic to GABAergic signaling has been implicated in several neuropsychiatric disorders including Tourette syndrome and attention-deficit/hyperactivity disorder (ADHD). In schizophrenia, decreases in parvalbumin (PV), somatostatin (Sst) and glutamic acid decarboxylase (GAD) RNA have been observed and seem to indicate a failure in maturation in PV and Sst neurons. In Tourette syndrome, which has a high level of comorbid ADHD, reduced numbers of parvalbumin expressing neurons have been observed in the basal ganglia of affected patients. In addition, polymorphisms in the GAD1 gene that codes for GAD67 protein have been associated with ADHD. We have examined whether mice with a disrupted Gad67 allele, the Gad67 GFP knock-in mice (Gad67-GFP^+/-), display abnormal locomotor behavior or altered anxiety behavior on the elevated plus maze. We found that Gad67-GFP^+/- mice displayed a mild hyperactivity compared to control littermates.