Mapping brain regions stimulation affects schizophrenia-like behaviour in the Polyl:C rat model of schizophrenia

Deep brain stimulation (DBS) has emerged as a powerful therapeutic strategy for the treatment of neuro-psychiatric disorders but also serves as an experimental approach in mapping brain regions and in understanding the interaction of neural circuits implicated in the pathogenesis of the respective disorders. So far, there is no report on the effects of DBS in patients suffering from schizophrenia or in respective animal models. The present study aimed at mapping brain regions in which bilateral DBS affects a cross-species behavioral deficit phenotypic of schizophrenia, i.e. prepulse inhibition (PPI) of an acoustic startle, in the Polyl:C rat model of schizophrenia. The medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), globus pallidus (GP), entopeduncular nucleus (EP), mediodorsal thalamus (MD), and subthalamic nucleus (STN) were selected DBS-targets. In each target, DBS was performed at different frequencies and current intensities. We found that DBS differentially affected PPI in both Polyl:C and naïve rats depending on stimulation target and parameter. This comparative mapping of brain areas in which DBS has therapeutic effects on schizophrenic deficits (mPFC, MD, GP, EP) and those areas at which DBS lacks such effects (STN) or is deleterious in both, schizophrenic and naïve rats (Nacc), allows drawing implications regarding the relevance of the investigated brain sites and functional circuits in the manifestation and therapy of schizophrenia symptoms.