BACKGROUND AND AIMS: NMDA receptor hypofunction is widely considered to contribute to the symptoms of schizophrenia. Although the pathophysiology of this disease remains unclear the nucleus accumbens (NAc) is one of the brain regions that has been widely implicated. Abnormal high frequency oscillations (HFO, 130–180 Hz) can be recorded in the rat NAc after injection of NMDA receptor antagonists. We have shown previously that reversible inhibition of the NAc by local infusion of tetrodotoxin reduces the amplitude of MK801-enhanced HFO indicating that this oscillation is generated by the intrinsic NAc network. Afferent regions powerfully modulate the activity of NAc neurons. However, it is not known to what extent HFO in the NAc may be driven by its afferent projections (ventral hippocampus, basolateral amygdala, prefrontal cortex and the vental tegmental area). METHODS: To address this issue, rats were implanted with electrodes in the NAc and guides targeted at these afferent sites. RESULTS: We found that infusion of TTX to the ventral tegmental area reduced the power of MK801-enhanced HFO on the ipsilateral but not contralateral side. In contrast infusion of TTX to the prefrontal cortex or ventral hippocampus had negligible effect MK801-enhanced HFO, although TTX infusion to the amygdala was found to produce a much weaker reduction in HFO power. CONCLUSIONS: These findings indicate that projections from the ventral tegmental area are capable of driving abnormal HFO in the NAc after injection of NMDA receptor antagonist. Further it suggests a loop involving these regions are required for the generation of HFO in rodent NAc. Project funded by the National Center of Science DEC-2011/03/B/ NZ4/03053.
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