Optogenetics and Fiber Photometry

Our Center faculty use state-of-the-art optogenetic and fiber photometry tools. Optogenetics describes the ability to regulate the activity of a protein with light. In its most commonly used version, mutant forms of non-mammalian ion channels or pumps that are activated by specific wavelengths of light are expressed in neurons and used to control the activity those cells in vivo. Channelrhodopsin 2 (ChR2) is used to activate neurons, while halorhodopsin (NpHR) or a related protein is used to inhibit neurons. In this way, it is possible to directly demonstrate what role a particular change in neuronal activity plays in depression-related phenomena. Center faculty are leading the field in using optogenetic tools to decipher the neural circuitry of mood regulation. We also used chemogenetic tools, which provide some advantages under certain circumstances.

We are also pioneering the use of fiber photometry which enables the measurement of Ca2+ signals within a given cell type of a given brain region in an awake, behaving animal. This is a major advance since it tells us how a neuronal type is responding during a behavioral task, as opposed to slice recordings which tell us about a cell's intrinsic excitability. Together, the two approaches provide an exquisite view of how a molecular/cellular adaptation in a cell type alters that cell's function. While fiber photometry does not provide information about individual neurons, it is an ideal method for this Center, since it enables us to test the influence of a given molecular adaptation in a single neuronal cell type on the integrated function of that subpopulation of neurons in awake, behaving animals.