PMID- 33674659
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Mar 5
TI  - Population imaging discrepancies between a genetically-encoded calcium indicator 
      (GECI) versus a genetically-encoded voltage indicator (GEVI).
PG  - 5295
LID - 10.1038/s41598-021-84651-6 [doi]
LID - 5295
AB  - Genetically-encoded calcium indicators (GECIs) are essential for studying brain 
      function, while voltage indicators (GEVIs) are slowly permeating neuroscience. 
      Fundamentally, GECI and GEVI measure different things, but both are advertised as 
      reporters of "neuronal activity". We quantified the similarities and differences 
      between calcium and voltage imaging modalities, in the context of population 
      activity (without single-cell resolution) in brain slices. GECI optical signals 
      showed 8-20 times better SNR than GEVI signals, but GECI signals attenuated more 
      with distance from the stimulation site. We show the exact temporal discrepancy 
      between calcium and voltage imaging modalities, and discuss the misleading 
      aspects of GECI imaging. For example, population voltage signals already 
      repolarized to the baseline (~ disappeared), while the GECI signals were still 
      near maximum. The region-to-region propagation latencies, easily captured by GEVI 
      imaging, are blurred in GECI imaging. Temporal summation of GECI signals is 
      highly exaggerated, causing uniform voltage events produced by neuronal 
      populations to appear with highly variable amplitudes in GECI population traces. 
      Relative signal amplitudes in GECI recordings are thus misleading. In 
      simultaneous recordings from multiple sites, the compound EPSP signals in 
      cortical neuropil (population signals) are less distorted by GEVIs than by GECIs.
FAU - Zhu, Mei Hong
AU  - Zhu MH
AD  - Institute for Systems Genomics, Department of Neuroscience, UConn School of 
      Medicine, Farmington, CT, 06030, USA.
FAU - Jang, Jinyoung
AU  - Jang J
AD  - Institute for Systems Genomics, Department of Neuroscience, UConn School of 
      Medicine, Farmington, CT, 06030, USA.
FAU - Milosevic, Milena M
AU  - Milosevic MM
AD  - Institute for Systems Genomics, Department of Neuroscience, UConn School of 
      Medicine, Farmington, CT, 06030, USA.
AD  - Center for Laser Microscopy, Faculty of Biology, University of Belgrade, 11000, 
      Belgrade, Serbia.
FAU - Antic, Srdjan D
AU  - Antic SD
AD  - Institute for Systems Genomics, Department of Neuroscience, UConn School of 
      Medicine, Farmington, CT, 06030, USA. antic@uchc.edu.
LA  - eng
GR  - R21 AG064554/AG/NIA NIH HHS/United States
GR  - U01 NS099573/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210305
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Indicators and Reagents)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain/*diagnostic imaging/*metabolism
MH  - Calcium/*metabolism
MH  - Calcium Signaling/*genetics
MH  - Female
MH  - Indicators and Reagents
MH  - Male
MH  - Membrane Potentials/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurons/*metabolism
MH  - Signal-To-Noise Ratio
MH  - Voltage-Sensitive Dye Imaging/*methods
PMC - PMC7935943
COIS- The authors declare no competing interests.
EDAT- 2021/03/07 06:00
MHDA- 2021/12/21 06:00
PMCR- 2021/03/05
CRDT- 2021/03/06 05:39
PHST- 2021/01/11 00:00 [received]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/03/06 05:39 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/03/05 00:00 [pmc-release]
AID - 10.1038/s41598-021-84651-6 [pii]
AID - 84651 [pii]
AID - 10.1038/s41598-021-84651-6 [doi]
PST - epublish
SO  - Sci Rep. 2021 Mar 5;11(1):5295. doi: 10.1038/s41598-021-84651-6.