Neural discoordination of hippocampus and prefrontal cortex spike trains in a phencyclidine schizophrenia-related animal model

Cognitive disorganization a core symptom of schizophrenia that is the not well treated. The discoordination hypothesis asserts that the core deficit is caused by widespread neural discoordination in structures that include the prefrontal cortex (PFC) and hippocampus (HPC). The hypothesis predicts that the psychotomimetic phencyclidine (PCP) induces neural discoordination. We tested this prediction by measuring the coordination of single unit spike trains recorded from the dorsal HPC (dHPC) and the medial PFC (mPFC). We examined the pair-wise correlations of spike trains within each structure as well as between the two regions. We simultaneously recorded ensembles of single unit activity as well as local field potentials (LFP; 1-300 Hz) from the dHPC and mPFC in urethane-anaesthetized rats. PCP (5mg/kg, i.p) or saline was injected after a 30-min baseline recording. Cell-pair coactivity was analyzed by Kendall's correlation. Correlations were divided into 3 categories according to whether they were positively coupled, negatively coupled, or firing independently during baseline. PCP injection increased spike train correlations of cell-pairs both within dHPC and cell pairs between dHPC and mPFC that were initially negatively or independently correlated. To assess which brain area drove this PCP-induced increase of coupling, we evaluated the information transfer between the dHPC and mPFC using normalized transfer entropy. PCP induced neural discoordination within the dHPC network and between the dHPC and mPFC networks, which supports a prediction of the discoordination hypothesis. These results provide a rationale and method for developing a high-throughput assay for procognitive antipsychotics, which should attenuate the PCP-induced neural discoordination.