Imaging Neurotransmitter and Neuromodulator Dynamics In Vivo with Genetically Encoded Indicators

The actions of neuromodulation are thought to mediate the ability of the mammalian brain to dynamically adjust its functional state in response to changes in the environment. Altered neurotransmitter (NT) and neuromodulator (NM) signaling is central to the pathogenesis or treatment of many human neurological and psychiatric disorders, including Parkinson’s disease, schizophrenia, depression, and addiction. To reveal the precise mechanisms by which these neurochemicals regulate healthy and diseased neural circuitry, one needs to measure their spatiotemporal dynamics in the living brain with great precision. Here, we discuss recent development, optimization, and applications of optical approaches to measure the spatial and temporal profiles of NT and NM release in the brain using genetically encoded sensors for in vivo studies. Sabatini and Tian review recent progress in developing genetically encoded neurotransmitter indicators. They also discuss practical considerations for both sensor developers and end users in terms of sensor design, optimization, characterization, and implementation for in vivo studies.