Optogenetic approaches for investigating neural pathways implicated in schizophrenia and related disorders

摘要

Optogenetic approaches have been rapidly adopted by neuroscientists in order to control the activity of neurons with high temporal, spatial and genetic specificity. By expressing light-sensitive microbial opsins within a genetically-specified population of neurons, flashes of light can be used to activate these opsins and thereby modulate the targeted cells in a spatially and temporally defined manner. Thus, optogenetics can be used to activate very specific sets of neurons or projections at particular times, either within freely behaving animals, or in reduced preparations such as brain slices. These techniques are ideally suited for dissecting complex interactions within neuronal circuits, and for testing ideas about how changes in these circuits might contribute to abnormal behaviors in the context of neuropsychiatric disorders. Here, we review several studies that have used optogenetics to dissect circuits implicated in schizophrenia, and elucidate the ways in which specific components of these circuits may contribute to normal or abnormal behavior. Specifically, optogenetics can be used to label and excite neurons that express particular genes, in order to study how they interact with other neurons and/or modulate behavior. Optogenetics can also be used to study changes in these interactions or behavioral effects following genetic manipulations. In this way, optogenetics may serve to 'fill in the gaps' between genes, circuits and behavior, in a manner that should help to translate the rapidly growing list of genes associated with neuropsychiatric disorders into specific pathophysiological mechanisms.