Abstract Body

Aims: Aberrant beta and gamma frequency oscillations are reported in patients with schizophrenia, alongside impaired working memory and attention. Additionally, increased neuroinflammation is reported in post-mortem tissue. Beta (20-30Hz) and gamma (30-80Hz) oscillations can be recorded from the rat anterior cingulate cortex (ACC) and hippocampus (HPC) in vitro. Cognitive and network dysfunction can be modelled in rodents using the NMDA receptor antagonist phencyclidine (PCP) and in vivo studies suggest sigma-1 receptor (σ1R) activation may reverse these deficits. However, the mechanism by which PCP causes disruption of oscillations, and the effects of PCP and σ1R modulation on network activation and neuroinflammation are unknown.

Methods: Rat ACC/HPC slices were prepared by standard methods and transferred to an interface chamber for electrophysiological recording. Network oscillations were evoked using bath-applied kainate. PCP and/or σ1R agonist PRE-084, were bath applied with or without kainate. After recording, slices were re-sectioned and immunostained for reactive astrocyte marker GFAP.

Results: PCP significantly increased the power of stable beta/gamma oscillations and slowed the oscillation frequency. However, the σ1R agonist PRE-084 had no effect on network oscillations. Exposing slices to PCP, versus kainate alone, showed a marked increase in reactive astrocytes. Our preliminary data suggests this PCP-evoked neuroinflammatory response was reduced by pre-application of PRE-084.

Conclusions: Our data suggests that the NMDA-R antagonist PCP induces an abnormally large oscillation and increases neuroinflammation, whilst the σ1R agonist PRE-084 reduces PCP’s neuroinflammatory effect. Further investigation is required to better understand the interplay between these two receptors and their effects on cognitive impairment.