Abnormal integration of activity across brain regions has been suggested to be an important pathophysiological mechanism underlying schizophrenia. Although this hypothesis has gained support from patient studies it nevertheless remains unclear how such dysconnectivity is manifest at the level of individual neurons and how it relates to the genetic risk factors for the disease. I will discuss experiments that aim to address these questions by simultaneously recording neural activity from the hippocampus and prefrontal cortex in mice carrying the 22q11.2 microdeletion, one of the major genetic risk factors for schizophrenia. These recordings were made while the mice performed a task requiring working memory, a cognitive function that is disrupted in the disease and requires the interaction between the hippocampus and the prefrontal cortex. The results of these experiments provide clues about how genetic mutations that predispose to the schizophrenia may alter network function in the brain and thus impair cognition and behavior.