• Postnatal NMDA receptor deletion confined to corticolimbic GABAergic neurons abolishes drug-induced gamma oscillation in adult mouse brain.

K NAKAO, JE BELFORTE, K NAKAZAWA

New Orleans USA

Congreso; Reunion Anual de la Society for Neuroscience; 2010

Gamma band (30-80 Hz) neural synchronization has been suggested to be associated with many sensory and cognitive functions, and may be important for cortico-cortical communication for integration of information. Schizophrenia patients often display abnormalities in both cognitive functioning and gamma band activity. Therefore, synchronous gamma activity may provide a direct window into schizophrenic disintegration. Recently, we characterized a mouse strain in which the essential NR1 subunit (Grin1) of the NMDA receptor (NMDAR) was selectively eliminated in 40-50% of cortical and hippocampal interneurons in early postnatal development, which resulted in schizophrenia-like phenotypes after adolescence (Belforte, et al. 2010). In order to clarify whether NMDAR ablation restricted to corticolimbic GABAergic interneurons also impairs synchronous gamma coherence, we conducted local field potential (LFP) recoding in vivo. We used an awake-promoting drug, Modafinil (2-[(Diphenylmethyl) sulfinyl]acetamide), which is known to induce robust and persistent gamma band oscillatory activity in mouse cortex. We implanted nichrome electrodes in somatosensory cortex of adult male mice under anesthesia. A week after surgery, we recorded LFPs while the mice explored a small open field for 60 min before and after Modafinil administered by intraperitoneal injections. Fourier analysis of LFPs revealed that the while the magnitude at the gamma frequency in floxed-NR1 control mice (n = 5) was enhanced 30 min after Modafinil injection (100 mg/kg) while there was no such change in the mutant mice (n = 4, p<.02 vs controls). These results suggested that postnatal GABAergic neuron-restricted NMDAR hypofunction results in an impairment in synchronous gamma oscillation generation. The present data may help in understanding the neural processing in schizophrenic disintegration. Analysis of physiological (spontaneous) gamma oscillatory activity from the mutant mouse brains is underway.