Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Science. 2018 Jun 29;360(6396):eaat4422. doi: 10.1126/science.aat4422. Epub 2018 May 31.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biosensing Techniques*
  • Calcium / analysis
  • Calcium / metabolism
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / metabolism*
  • Corpus Striatum
  • Dopamine / analysis
  • Dopamine / metabolism*
  • Genetic Engineering
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Humans
  • Learning
  • Mice
  • Neuroimaging / methods*
  • Neurons / physiology
  • Neurotransmitter Agents / analysis
  • Neurotransmitter Agents / metabolism*
  • Optogenetics*
  • Receptors, Dopamine D1 / chemistry
  • Receptors, Dopamine D1 / genetics
  • Serotonin / analysis
  • Serotonin / metabolism


  • DRD1 protein, human
  • Neurotransmitter Agents
  • Receptors, Dopamine D1
  • Green Fluorescent Proteins
  • Serotonin
  • Calcium
  • Dopamine