Cross-species assessments of motor and exploratory behavior related to bipolar disorder

Abstract

Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the human behavioral pattern monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders.

Figure 1

The mouse Behavior Pattern Monitor (mBPM) (A) and Human Behavior Pattern Monitor (B). The mBPM consists of a 30.5 by 61 cm Plexiglas chamber equipped with 3 floor holes and 8 wall holes that serve as objects to stimulate exploratory behavior. Mouse locomotor activity is monitored by a grid of 12 by 24 infrared photobeams placed 1 cm above the floor. Additional photobeams are situated in each hole to record holepokes. The hBPM is a 2.7 by 4.3 meter room that serves as a novel environment for human subjects who receive no explicit instructions or directions during the test. The room contains several 11 small objects dispersed across several items of furniture, but does not include a chair. Motor activity and object interactions are recorded during the 15 minute testing session by a digital camera concealed in the ceiling.