Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo
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Abstract
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Our improved red fluorescent DA sensors performed as well as295their corresponding green fluorescent counterparts in terms of their sensitivity at detecting DA signals, thereby296narrowing the performance gap between red and green fluorescent DA sensors
This is very impressive and useful! Well done!
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Although most areas had no response
I'm surprised and intrigued that such a small portion (<10%) of the FOV showed changes in dopamine.It seem challenging to understand heterogeneity patterns with such a small proportion of responses. Do you think this is due to the expression level or sensitivity of the indicator? Perhaps a cortical region (like prefrontal cortex) or different stimulus (perhaps a rewarding paradigm) would allow for a larger dopaminergic response and clearer analysis?
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We found that rDA2m and eCB2.0 had reproducible, time-locked transient236increases in fluorescence upon delivery of a 2-s foot shock; moreover, although the signal produced by eCB2.0 was237similar between hemispheres, the signal produced by rDA2m was approximately twice as large as the signal238produced by rDA1m (Fig. 4i-l).
The timing here is really interesting! Particularly from panels i-k it appears the dopamine sensor fluorescence remains elevated above pre-footshock levels. Is this a property of the sensors or do you believe this to be biological in nature? How does it effect the calculation of Toff in this paradigm? Does it inform your interpretation of the "fast" dopamine vs "slow" endocannabinoid singals?
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were closely correlated227with the DA signal (Fig. 4e and 4f)
This is an awesome result! The correlation is so strong, how much of the correlation do you think is directly due to dopamine signaling vs other effects? Do you think there is any cross-talk between the channels or other effects increasing the observed correlation?
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Thus, these sensors are suitable for long-term monitoring of dopaminergic activit
Do these results have implications for using the Rdlight1 or rDA3 for experiments involving dual-color imaging and/or optogenetics?
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Fig. 2f
The specificity of this dopamine sensor is great overall, and it's good to see higher sensitivity to dopamine compared with norepinephrine! Could you also talk about the variability between individual cells and show the individual data points for this graph rather than just the mean +/- SEM? It would help me understand over what range and in what contexts I might expect some fluorescence due to norepinephrine.
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