Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator

AS. Abdelfattah, J. Zheng, A. Singh, YC. Huang, D. Reep, G. Tsegaye, A. Tsang, BJ. Arthur, M. Rehorova, CVL. Olson, Y. Shuai, L. Zhang, TM. Fu, DE. Milkie, MV. Moya, TD. Weber, AL. Lemire, CA. Baker, N. Falco, Q. Zheng, JB. Grimm, MC. Yip, D....

. 2023 ; 111 (10) : 1547-1563.e9. [pub] 20230403

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc23011426

Grant support
DP2 MH129956 NIMH NIH HHS - United States
F32 MH129149 NIMH NIH HHS - United States

The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, although with lower baseline fluorescence. In multiple in vitro and in vivo comparisons with its predecessor across multiple species, we found Voltron2 to be more sensitive to APs and subthreshold fluctuations. Finally, we used Voltron2 to study and evaluate the possible mechanisms of interneuron synchronization in the mouse hippocampus. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23011426
003      
CZ-PrNML
005      
20230801133033.0
007      
ta
008      
230718s2023 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.neuron.2023.03.009 $2 doi
035    __
$a (PubMed)37015225
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Abdelfattah, Ahmed S $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: ahmed_abdelfattah@brown.edu
245    10
$a Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator / $c AS. Abdelfattah, J. Zheng, A. Singh, YC. Huang, D. Reep, G. Tsegaye, A. Tsang, BJ. Arthur, M. Rehorova, CVL. Olson, Y. Shuai, L. Zhang, TM. Fu, DE. Milkie, MV. Moya, TD. Weber, AL. Lemire, CA. Baker, N. Falco, Q. Zheng, JB. Grimm, MC. Yip, D. Walpita, M. Chase, L. Campagnola, GJ. Murphy, AM. Wong, CR. Forest, J. Mertz, MN. Economo, GC. Turner, M. Koyama, BJ. Lin, E. Betzig, O. Novak, LD. Lavis, K. Svoboda, W. Korff, TW. Chen, ER. Schreiter, JP. Hasseman, I. Kolb
520    9_
$a The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, although with lower baseline fluorescence. In multiple in vitro and in vivo comparisons with its predecessor across multiple species, we found Voltron2 to be more sensitive to APs and subthreshold fluctuations. Finally, we used Voltron2 to study and evaluate the possible mechanisms of interneuron synchronization in the mouse hippocampus. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability.
650    _2
$a myši $7 D051379
650    _2
$a zvířata $7 D000818
650    _2
$a akční potenciály $x fyziologie $7 D000200
650    12
$a rodopsin $x genetika $7 D012243
650    12
$a angiotensin-konvertující enzym 2 $7 D000085962
650    _2
$a neurony $x fyziologie $7 D009474
650    _2
$a mutace $x genetika $7 D009154
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Zheng, Jihong $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Singh, Amrita $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Huang, Yi-Chieh $u Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan
700    1_
$a Reep, Daniel $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Tsegaye, Getahun $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Tsang, Arthur $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Arthur, Benjamin J $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Rehorova, Monika $u Department of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Olson, Carl V L $u Department of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Shuai, Yichun $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Zhang, Lixia $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Fu, Tian-Ming $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Milkie, Daniel E $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Moya, Maria V $u Department of Biomedical Engineering, Boston University, Boston, MA, USA
700    1_
$a Weber, Timothy D $u Department of Biomedical Engineering, Boston University, Boston, MA, USA
700    1_
$a Lemire, Andrew L $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Baker, Christopher A $u Allen Institute for Brain Science, Seattle, WA, USA
700    1_
$a Falco, Natalie $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Zheng, Qinsi $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Grimm, Jonathan B $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Yip, Mighten C $u George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
700    1_
$a Walpita, Deepika $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Chase, Martin $u Portland, OR, USA
700    1_
$a Campagnola, Luke $u Allen Institute for Brain Science, Seattle, WA, USA
700    1_
$a Murphy, Gabe J $u Allen Institute for Brain Science, Seattle, WA, USA
700    1_
$a Wong, Allan M $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Forest, Craig R $u George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
700    1_
$a Mertz, Jerome $u Department of Biomedical Engineering, Boston University, Boston, MA, USA
700    1_
$a Economo, Michael N $u Department of Biomedical Engineering, Boston University, Boston, MA, USA
700    1_
$a Turner, Glenn C $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Koyama, Minoru $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Lin, Bei-Jung $u Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan
700    1_
$a Betzig, Eric $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; Departments of Molecular and Cell Biology and Physics, Howard Hughes Medical Institute, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
700    1_
$a Novak, Ondrej $u Department of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
700    1_
$a Lavis, Luke D $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Svoboda, Karel $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Korff, Wyatt $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
700    1_
$a Chen, Tsai-Wen $u Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: chentw@nycu.edu.tw
700    1_
$a Schreiter, Eric R $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: schreitere@janelia.hhmi.org
700    1_
$a Hasseman, Jeremy P $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: hassemanj@janelia.hhmi.org
700    1_
$a Kolb, Ilya $u Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; GENIE Project Team, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address: kolbi@janelia.hhmi.org
773    0_
$w MED00003493 $t Neuron $x 1097-4199 $g Roč. 111, č. 10 (2023), s. 1547-1563.e9
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37015225 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230718 $b ABA008
991    __
$a 20230801133029 $b ABA008
999    __
$a ok $b bmc $g 1963688 $s 1197691
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 111 $c 10 $d 1547-1563.e9 $e 20230403 $i 1097-4199 $m Neuron $n Neuron $x MED00003493
GRA    __
$a DP2 MH129956 $p NIMH NIH HHS $2 United States
GRA    __
$a F32 MH129149 $p NIMH NIH HHS $2 United States
LZP    __
$a Pubmed-20230718
Back

Find record

Citation metrics

Archiving options