The dynamics of disordered dialogue: Prefrontal, hippocampal and thalamic miscommunication underlying working memory deficits in schizophrenia

Abstract

The prefrontal cortex is central to the orchestrated brain network communication that gives rise to working memory and other cognitive functions. Accordingly, working memory deficits in schizophrenia are increasingly thought to derive from prefrontal cortex dysfunction coupled with broader network disconnectivity. How the prefrontal cortex dynamically communicates with its distal network partners to support working memory and how this communication is disrupted in individuals with schizophrenia remain unclear. Here we review recent evidence that prefrontal cortex communication with the hippocampus and thalamus is essential for normal spatial working memory, and that miscommunication between these structures underlies spatial working memory deficits in schizophrenia. We focus on studies using normal rodents and rodent models designed to probe schizophrenia-related pathology to assess the dynamics of neural interaction between these brain regions. We also highlight recent preclinical work parsing roles for long-range prefrontal cortex connections with the hippocampus and thalamus in normal and disordered spatial working memory. Finally, we discuss how emerging rodent endophenotypes of hippocampal- and thalamo-prefrontal cortex dynamics in spatial working memory could translate into richer understanding of the neural bases of cognitive function and dysfunction in humans.