High frequency neuronal oscillatory abnormalities in the phospholipase C-β1 knockout mouse model of schizophrenia.

Background: Schizophrenia is a complex neuropsychiatric disorder characterised by psychoses, socioaffective disturbances and cognitive deficits. The phosphodiesterase enzyme phospholipase C-β1 (PLC-β1) has been reported to be reduced in post-mortem tissue of schizophrenia patients. Dysregulation of neuronal oscillations, particularly those in the higher frequency range, such as beta (12-30 Hz) and gamma (30-80 Hz), are also associated with this disorder. We investigated the influence of PLC-β1 gene deletion on cortical oscillatory activity and sensorimotor gating behavior.

Methods: Adult PLC-β1 knock-out (PLC-β1-/-) and wildtype C57Bl/6J control mice (total n=26) underwent surgical implantation of extradural electrodes to allow electrocorticography (ECoG) recordings. ECoG was recorded during prepulse inhibition (PPI) behavior sessions to measure ongoing and auditory-evoked electrophysiological responses. Mice were also pre-treated with antipsychotic drugs haloperidol (0.25mg/kg), clozapine (2.5mg/kg) and olanzapine (5mg/kg).

Results: PLC-β1-/- mice exhibited reduced PPI, and diminished power and phase synchrony of beta and gamma oscillatory responses to auditory stimuli, as well as elevated ongoing beta oscillations. Reductions in PPI were highly correlated with the power and phase synchrony of evoked oscillations. Clozapine and olanzapine ameliorated the PPI deficit in PLC-β1 -/- mice, but not the electrophysiology abnormalities.

Conclusions: PLC-β1 reduction leads to disturbances to beta and gamma oscillatory dynamics, and PPI behavior. The strong relationships between these measures demonstrate the importance of event-related oscillatory activity to sensorimotor gating behavior. However, dissociation of these measures observed in the drug studies suggests that abnormalities in neuronal networks may not necessarily need to be corrected for behavioral improvement.