Prepulse inhibition and genetic mouse models of schizophrenia

Abstract

Mutant mouse models related to schizophrenia have been based primarily on the pathophysiology of schizophrenia, the known effects of antipsychotic drugs, and candidate genes for schizophrenia. Sensorimotor gating deficits in schizophrenia patients, as indexed by measures of prepulse inhibition of startle (PPI), have been well characterized and suggested to meet the criteria as a useful endophenotype in human genetic studies. PPI refers to the ability of a non-startling "prepulse" to inhibit responding to the subsequent startling stimulus or "pulse." Because of the cross-species nature of PPI, it has been used primarily in pharmacological animal models to screen putative antipsychotic medications. As techniques in molecular genetics have progressed over the past 15 years, PPI has emerged as a phenotype used in assessing genetic mouse models of relevance to schizophrenia. In this review, we provide a selected overview of the use of PPI in mouse models of schizophrenia and discuss the contribution and usefulness of PPI as a phenotype in the context of genetic mouse models. To that end, we discuss mutant mice generated to address hypotheses regarding the pathophysiology of schizophrenia and candidate genes (i.e., hypothesis driven). We also briefly discuss the usefulness of PPI in phenotype-driven approaches in which a PPI phenotype could lead to "bottom up" approaches of identifying novel genes of relevance to PPI (i.e., hypothesis generating).