Genetically encoded fluorescent sensors for imaging neuronal dynamics in vivo

Abstract

The brain relies on many forms of dynamic activities in individual neurons, from synaptic transmission to electrical activity and intracellular signaling events. Monitoring these neuronal activities with high spatiotemporal resolution in the context of animal behavior is a necessary step to achieve a mechanistic understanding of brain function. With the rapid development and dissemination of highly optimized genetically encoded fluorescent sensors, a growing number of brain activities can now be visualized in vivo. To date, cellular calcium imaging, which has been largely used as a proxy for electrical activity, has become a mainstay in systems neuroscience. While challenges remain, voltage imaging of neural populations is now possible. In addition, it is becoming increasingly practical to image over half a dozen neurotransmitters, as well as certain intracellular signaling and metabolic activities. These new capabilities enable neuroscientists to test previously unattainable hypotheses and questions. This review summarizes recent progress in the development and delivery of genetically encoded fluorescent sensors, and highlights example applications in the context of in vivo imaging.

Keywords: fast neurotransmission imaging; gene delivery in brain; genetically encoded sensors; imaging neuromodulation; in vivo imaging.

Figure 1.. Fast and slow signaling pathways

Schematic representation of fast--defined by ionotropic receptor signaling—and slow—defined by metabotropic receptor signaling pathways—modes of neuronal information transmission with approximate timescale of each signaling step in parentheses. Metabolic signaling (e.g. ATP/ADP, NADH/NAD+) operates both presynaptically and postsynaptically in concert with the fast and slow signaling pathways.