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.
Highlights
Schizophrenia is a complex neurological disorder that affects approximately one percent of the population worldwide (Jablensky, 2000; McGrath et al, 2008), and is a leading contributor of the global disease burden (Lopez et al, 2006)
We have discussed how disruptions in these oscillatory mechanisms could lead to the kind of disorganized processing and functional disintegration that is observed in schizophrenia, to the degree that it might underlie some of the core features of the disorder, the disruption of episodic memory and planning processes
While dysfunction in a number of different brain regions is likely to occur in schizophrenia, we have chosen to focus on the hippocampus because of its role in encoding sequential information across time and space
Summary
Schizophrenia is a complex neurological disorder that affects approximately one percent of the population worldwide (Jablensky, 2000; McGrath et al, 2008), and is a leading contributor of the global disease burden (Lopez et al, 2006). Neuregulin signaling has been shown to be important for the synchronization of network activity in the prefrontal cortex in vivo (Hou et al, 2014; Barz et al, 2016), and increases of induced gamma power that occur in wildtype animals were absent in mutant mice lacking ErbB4 receptors on interneurons located in frontal regions (Hou et al, 2014).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
