Imaging chemical neurotransmission with genetically encoded fluorescent sensors

ACS Chem Neurosci. 2015 Jan 21;6(1):84-93. doi: 10.1021/cn500280k. Epub 2015 Jan 13.


A major challenge in neuroscience is to decipher the logic of neural circuitry and to link it to learning, memory, and behavior. Synaptic transmission is a critical event underlying information processing within neural circuitry. In the extracellular space, the concentrations and distributions of excitatory, inhibitory, and modulatory neurotransmitters impact signal integration, which in turn shapes and refines the function of neural networks. Thus, the determination of the spatiotemporal relationships between these chemical signals with synaptic resolution in the intact brain is essential to decipher the codes for transferring information across circuitry and systems. Here, we review approaches and probes that have been employed to determine the spatial and temporal extent of neurotransmitter dynamics in the brain. We specifically focus on the design, screening, characterization, and application of genetically encoded indicators directly probing glutamate, the most abundant excitatory neurotransmitter. These indicators provide synaptic resolution of glutamate dynamics with cell-type specificity. We also discuss strategies for developing a suite of genetically encoded probes for a variety of neurotransmitters and neuromodulators.

Keywords: Neurotransmitter; fluorescent sensor; genetically encoded indicators; iGluSnFR; neuromodulator; optical probes; synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Diagnostic Imaging*
  • Glutamic Acid / metabolism
  • Humans
  • Luminescent Proteins* / genetics
  • Luminescent Proteins* / metabolism
  • Microscopy, Fluorescence
  • Models, Molecular
  • Neurotransmitter Agents / genetics
  • Neurotransmitter Agents / metabolism*


  • Luminescent Proteins
  • Neurotransmitter Agents
  • Glutamic Acid