Nat. Meth. 10, 162–170 (2013)

Credit: NATURE METHODS

Glutamate receptors are critical for synaptic transmission and regulation of neuronal activity. Interrogating the direct determinants of neural circuit function thus requires sensors capable of monitoring rapid neurotransmitter transients in intact preparations. To overcome limitations of existing glutamate biosensors, Marvin et al. fused a bacterial periplasmic glutamate-binding protein to circularly permuted GFP such that the sensor responds to glutamate with green light. iGluSnFR is specific for glutamate over other amino acids, neurotransmitters or drugs and has a high signal-to-noise ratio. In cultured neurons and astrocytes, iGluSnFR responded to glutamate release from single electrical pulses. Glutamate uncaging in brain slices calibrated the sensor signal to physiological neurotransmission levels. In mouse retina in vitro, Caenorhabditis elegans worms, and zebrafish larvae and rat motor cortex in vivo, iGluSnFR reported glutamate transients in single neurons, dendritic spines and dendritic branches in awake, active animals, demonstrating its utility for monitoring excitatory synaptic transmission. iGluSnFR and sensors for other neurotransmitters could prove useful in combination with calcium imaging to fully document how neuronal signaling events integrate to brain activity.