Independent Optical Excitation of Distinct Neural Populations

By Nathan C. Klapoetke, Yasunobu Murata, Sung Soo Kim, S. Pulver, Amanda Birdsey-Benson, Y. Cho, Tania K Morimoto, A. Chuong, E. Carpenter, Zhijian Tian and 11 more. 2014

2,160 citations recorded by the source corpus.

Optogenetic tools enable examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the study of how different synapses or pathways interact to encode information in the brain. Here we describe two channelrhodopsins, Chronos and Chrimson, discovered through sequencing and physiological characterization of opsins from over 100 species of alga. Chrimson's excitation spectrum is red shifted by 45 nm relative to previous channelrhodopsins and can enable experiments in which red light is preferred. We show minimal visual system–mediated behavioral interference when using Chrimson in neurobehavioral studies in Drosophila melanogaster. Chronos has faster kinetics than previous channelrhodopsins yet is effectively more light sensitive. Together these two reagents enable two-color activation of neural spiking and downstream synaptic transmission in independent neural populations without detectable cross-talk in mouse brain slice.

Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems

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Citations in the corpus

Dopaminergic neurons write and update memories with cell-type-specific rules (2016, methodology): “Crosses of split-GAL4 lines for DANs (Aso et al., 2014a) and 20xUAS-CsChrimson-mVenus in attP18 (Klapoetke et al., 2014) were kept on standard cornmeal food supplemented with retinal (0.2 mM all-trans-retinal prior to eclosion and then 0.4 mM) at 22˚C at 60% relative humidity in the dark.”
Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila (2014, methodology): “The following constructs were used for activating or silencing neuronal function: 5XUAS-CsChrimsonmVenus (attP18), 10XUAS-CsChrimson-mVenus (attP18), 20XUAS-CsChrimson-mVenus (attP18) (Klapoetke et al., 2014); pJFRC124-20XUAS-IVS-dTrpA1 (attP18); 10XUAS-dTrpA1 (attP16) (Hamada et al.”
A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters (2018, neutral): “4 –6).”
Heterosynaptic plasticity underlies aversive olfactory learning in Drosophila (2015, neutral): “To maximally restrict expression of the optogenetic exciter CsChrimson (Klapoetke et al., 2014), we created the split-GAL4 line MB320C, which labels a single PPL1-g1pedc neuron (Figure S1A).”
Thalamic neuromodulation and its implications for executive networks (2014, methodology): “Recording from thalamic dendrites is feasible (Williams and Stuart, 2000), and recent advancements in multicolor optogenetics (Klapoetke et al., 2014) allow the specific manipulation of multiple modulator populations.”
A Higher Brain Circuit for Immediate Integration of Conflicting Sensory Information in Drosophila. (2015, methodology): “We expressed the red light-sensitive channelrhodopsin CsChrimson [22] in MBONs under the control of MB011B and MB002B (MB-Split-Gal4;UAS-CsChrimson) to activate these neurons exclusively in the presence of red light.”
Closed-loop and activity-guided optogenetic control. (2015, positive): “…approach to optogenetic inhibition. from Mattis et al., 2012; Hochbaum et al., 2014; Inoue et al., 2015; Wu et al., 2013; Yizhar et al., 2011b; Klapoetke et al., 2014; Lin et al., 2013; Akerboom et al., 2012, 2013; Chen et al., 2013c; Berndt et al., 2014; Gradinaru et al., 2010; Chuong et…”
Origins of Cell-Type-Specific Olfactory Processing in the Drosophila Mushroom Body Circuit. (2017, positive): “The following stocks were used: VT33006-Gal4 (attP2) (von Philipsborn et al., 2011); VT43924-Gal4 (attP2) and APL-Gal4 (VT43924-Gal4 (attP2), UAS-Gal4) (Wu et al., 2013); Mz19-Gal4 (Ito et al., 1998; Tanaka et al., 2004), OK107-Gal4 (Connolly et al., 1996), UAS-ReaChR::Citrine (attP40) (Inagaki et a”
A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality (2018, neutral): “These include Ai90 (with channelrhodop-sin Chronos-GFP) (Klapoetke et al., 2014), Ai133 (with an electron microscopy tag ssAPEX2tm) (Lam et al., 2015), Ai134 (with channelrhodopsin ChR2(H134R)-YFP), and Ai136 (with chan-nelrhodopsin ReaChR-YFP) (Lin et al., 2013) (Figure 2B).”