Imaging fluorescent proteins is a common method to assess the organization and function of neural circuits. However, overlapping fluorescence from nearby axons and dendrites can make it difficult to pick out signals arising from individual neurons. Here, Chen et al. and Shemesh et al. show that confining fluorescent proteins to the cell body can limit such cross-contamination. To improve the resolution of neuronal calcium imaging, Shemesh et al. screened a series of proteins composed of GCaMP calcium indicators fused to various peptides and identified two ‘somatic GCaMPs’ with expression that was restricted to the cell body. Taking a similar approach, Chen et al. tethered a GCaMP indicator directly to the ribosome, a macromolecule found within the cell body. In both studies, there was a reduction in the contaminating fluorescent signal from the neuropil, allowing for a better visualization of the somatic signal. The authors demonstrated the advantages of this approach for the assessment of calcium dynamics in cultures, slices and in vivo experiments. Chen et al. further showed that tethering a GFP-binding nanobody to the ribosome can also boost somatic fluorescence in GFP reporter mice, providing additional support for the use of somatic targeting in cellular imaging.
Chen, Y. et al. Soma-targeted imaging of neural circuits by ribosome tethering. Neuron https://doi.org/10.1016/j.neuron.2020.05.005 (2020)
Shemesh, O. A. et al. Precision calcium imaging of dense neural populations via a cell-body-targeted calcium indicator. Neuron https://doi.org/10.1016/j.neuron.2020.05.029 (2020)
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Whalley, K. Soma trapping sharpens signals. Nat Rev Neurosci 21, 451 (2020). https://doi.org/10.1038/s41583-020-0345-8