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Abstract

Schizophrenia is a chronic, debilitating disorder with diverse symptomatology, including cognitive and motivational impairments. Disorganized temporal processing may be a trait marker of the disorder, with relevance to several classical symptoms. Activity in the hippocampus, a region that encodes sequential information across time and space, has been shown to be disrupted in schizophrenia. Here we examined hippocampal phase precession, in a rodent Maternal Immune Activation (MIA) model of schizophrenia risk. Phase precession describes how individual place cells systematically advance their firing phase against the background theta oscillation as an animal moves through the cell’s place field. Importantly, phase precession provides a mechanism by which the sequential order of progression across overlapping place fields can be compressed into a single theta cycle (known as a ‘theta sequence’), a timescale suitable for the induction of synaptic plasticity and the storage of sequential information. However, accurate storage requires phase precession of individual cells to be coordinated across cell assemblies so that the phase onset and slope of precession is relatively consistent across cells. Without such coordination, theta sequences may become disorganized. Electrodes were implanted into the pyramidal cell layer of dorsal CA1 in mature rats that were the offspring of dams that had received either a single MIA (Poly I:C) or control injection (saline) during mid-gestation (GD15). Both cell firing activity and local field potentials were recorded as rats ran around a rectangular track. Our results showed that the within-cell slope and intensity of phase precession were similar for both groups, suggesting that the MIA intervention did not alter the ability to precess at the level of individual cells. However, a striking difference was observed across the population of MIA cells regarding the onset and subsequent phase of precession, with much greater between-cell phase variability in these animals. Furthermore, ‘theta sequences’ were significantly disorganized in MIA rats when compared to controls, most likely as a result of this variability. Together, these results strongly suggest that the coordination of activity across precessing cells is compromised in MIA animals, likely contributing to more disorganized processing and storage of sequential information. This finding provides, for the first time, evidence of a biological-level mechanism to explain disorganized temporal processing in schizophrenia, which could contribute to thought disorder, misattributions of agency or control, and impaired episodic memory and future planning.