Journal Article

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Liang, Ruqiang, Zhong, Haining, Xiong, Wei-Hong, von Zastrow, Mark, Gradinaru, Viviana, Tian, Lin, Dombeck, Daniel, Patriarchi, Tommaso, Folk, Robert W., Jang, Min Jee, Williams, John T., Howe, Mark W., Marley, Aaron, Merten, Katharina, Nimmerjahn, Axel, Cho, Jounhong Ryan, Broussard, Gerard Joey

2018

Overview

Neuromodulator release alters the function of target circuits in poorly known ways. An essential step to address this knowledge gap is to measure the dynamics of neuromodulatory signals while simultaneously manipulating the elements of the target circuit during behavior. Patriarchi et al. developed fluorescent protein–based dopamine indicators to visualize spatial and temporal release of dopamine directly with high fidelity and resolution. In the cortex, two-photon imaging with these indicators was used to map dopamine activity at cellular resolution. Science , this issue p. eaat4422 Genetically encoded indicators allow optical measurement of dopamine release in vivo at high spatiotemporal resolution. Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires spatiotemporally precise measurement of neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in mouse striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in mouse cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.

• Publisher: The American Association for the Advancement of Science
• Subject: Addictions / Animals / Biosensing Techniques / Brain / Calcium / Calcium - analysis / Calcium - metabolism / Calcium imaging / Cerebral Cortex - chemistry / Cerebral Cortex - metabolism / Circuits / Coding / Corpus Striatum / Cortex (motor) / Disorders / Dopamine / Dopamine - analysis / Dopamine - metabolism / Drug abuse / Drug addiction / Drug dependence / Dynamics / Electrical stimuli / Fluorescence / Functional analysis / Genetic code / Genetic Engineering / Genetics / Green fluorescent protein / Green Fluorescent Proteins - chemistry / Green Fluorescent Proteins - genetics / High resolution / Human behavior / Humans / Image resolution / Indicators / Information processing / Learning / Medical imaging / Melatonin / Mental depression / Mental disorders / Mice / Motor skill learning / Motor task performance / Narcotics / Neostriatum / Neural coding / Neuroimaging / Neuroimaging - methods / Neuromodulation / Neurons - physiology / Neuropeptides / Neurotransmitter Agents - analysis / Neurotransmitter Agents - metabolism / Norepinephrine / Opioids / Optogenetics / Organic chemistry / Parkinson's disease / Pharmacology / Proteins / Receptors, Dopamine D1 - chemistry / Receptors, Dopamine D1 - genetics / Recording / Schizophrenia / Sensorimotor integration / Sensors / Serotonin / Serotonin - analysis / Serotonin - metabolism / Stimulation / Stimuli / Temporal lobe