This is a repository copy of Hippocampal sequencing mechanisms are disrupted in a maternal immune activation model of schizophrenia risk.

No abstract

Schizophrenia is a chronic, debilitating disorder with diverse symptomatology, including disorganized cognition and behavior. Despite considerable research effort, we have only a limited understanding of the underlying brain dysfunction. In this article, we review the potential role of oscillatory circuits in the disorder with a particular focus on the hippocampus, a region that encodes sequential information across time and space, as well as the frontal cortex. Several mechanistic explanations of schizophrenia propose that a loss of oscillatory synchrony between and within these brain regions may underlie some of the symptoms of the disorder. We describe how these oscillations are affected in several animal models of schizophrenia, including models of genetic risk, maternal immune activation (MIA) models, and models of NMDA receptor hypofunction. We then critically discuss the evidence for disorganized oscillatory activity in these models, with a focus on gamma, sharp wave ripple, and theta activity, including the role of cross-frequency coupling as a synchronizing mechanism. Finally, we focus on phase precession, which is an oscillatory phenomenon whereby individual hippocampal place cells systematically advance their firing phase against the background theta oscillation. Phase precession is important because it allows sequential experience to be compressed into a single 120 ms theta cycle (known as a ‘theta sequence’). This time window is appropriate for the induction of synaptic plasticity. We describe how disruption of phase precession could disorganize sequential processing, and thereby disrupt the ordered storage of information. A similar dysfunction in schizophrenia may contribute to cognitive symptoms, including deficits in episodic memory, working memory, and future planning.

This is a repository copy of Aberrant phase precession of lateral septal cells in a maternal immune activation model of schizophrenia risk may disrupt the integration of location with reward.

Maternal immune activation (MIA) is a risk factor for schizophrenia and other neurodevelopmental disorders. MIA in rats models a number of the brain and behavioral changes that are observed in schizophrenia, including impaired memory. Recent studies in the MIA model have shown that the firing of the hippocampal place cells that are involved in memory processes appear relatively normal, but with abnormalities in the temporal ordering of firing. In this study, we re‐analyzed data from prior hippocampal electrophysiological recordings of MIA and control animals to determine whether temporal dysfunction was evident. We find that there is a decreased ratio of slow to fast gamma power, resulting from an increase in fast gamma power and a tendency toward reduced slow gamma power in MIA rats. Moreover, we observe a robust reduction in spectral coherence between hippocampal theta and both fast and slow gamma rhythms, as well as changes in the phase of theta at which fast gamma occurs. We also find the phasic organization of place cell phase precession on the theta wave to be abnormal in MIA rats. Lastly, we observe that the local field potential of MIA rats contains more frequent sharp‐wave ripple events, and that place cells were more likely to fire spikes during ripples in these animals than control. These findings provide further evidence of desynchrony in MIA animals and may point to circuit‐level changes that underlie failures to integrate and encode information in schizophrenia.