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Improved Version of ChETA Promotes Aggression in the Medial Amygdala

Hu, Rongfeng K. and Chen, Patrick B. and Berndt, André and Anderson, David J. and Hong, Weizhe (2022) Improved Version of ChETA Promotes Aggression in the Medial Amygdala. . (Unpublished)

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The development of optogenetic tools has significantly advanced our understanding of neural circuits and behavior. The medial amygdala, posterior dorsal subdivision (MeApd) is part of a distributed network controlling social behaviors such as mating and aggression. Previous work showed that activation of GABAergic neurons in mouse MeApd using channelrodopsin-2 (ChR2^(H134R)) promoted aggression. In a recent study, Baleisyte et al. (2022) confirmed these findings using the same reagents (i.e. ChR2^(H134R)), but also reported that a different ChR2 variant with faster kinetics—ChETA—inhibited rather than promoted aggression when high laser power, long duration photostimulation conditions were used. As ChETA is known to have a substantially lower photocurrent than ChR2 and other opsins, an improved version of ChETA (i.e. ChR2^(E123T/T159C); ChETA_(TC)) was subsequently developed. ChETATC has larger photocurrents than the original ChETA while maintaining fast kinetics and low plateau depolarization. Here we show that activating MeApd GABAergic neurons using the improved ChETATC promotes aggression, similar to ChR2^(H134R), suggesting that the results obtained using the original ChETA are not due to a difference in channel kinetics. Furthermore, we found that ChETATC is capable of driving a rapid onset of aggression within 200-300 milliseconds of stimulation, suggesting that this effect reflects direct activation of MeApd GABAergic neurons. We conclude that the different behavioral phenotypes observed using the original ChETA vs. ChETA_(TC) and ChR2 likely reflects the weaker photocurrents in ChETA vs. other opsins, and/or the long duration/high power photostimulation conditions used with ChETA. Consistent with this conclusion, the results obtained using ChR2 or ChETA_(TC) are complementary to findings from loss-of-functions experiments using optogenetic inhibition, chemogenetic inhibition, and neuronal ablation. These data support a positive-acting role of MeApd Vgat+ neurons in aggression. Our findings, in conjunction with studies of Berndt et al. (2011), suggest that the improved ChETATC should be used when faster kinetics than ChR2 offers are required.

Item Type:Report or Paper (Discussion Paper)
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URLURL TypeDescription Paper
Hu, Rongfeng K.0000-0002-0206-5284
Berndt, André0000-0003-4758-5598
Anderson, David J.0000-0001-6175-3872
Hong, Weizhe0000-0003-1523-8575
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Version 1 - June 6, 2022; Version 2 - July 2, 2022. We thank Olexiy Kochubey and Ralf Schneggenburger (EPFL) for providing feedback on data described in this manuscript. The authors have declared no competing interest.
Record Number:CaltechAUTHORS:20220607-425158000
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Official Citation:Improved Version of ChETA Promotes Aggression in the Medial Amygdala. Rongfeng K. Hu, Patrick B. Chen, André Berndt, David J. Anderson, Weizhe Hong. bioRxiv 2022.06.05.493862; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:115050
Deposited By: George Porter
Deposited On:08 Jun 2022 15:51
Last Modified:12 Jul 2022 19:31

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