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In vivo two-photon microscopy reveals sensory-evoked serotonin (5-HT) release in adult mammalian neocortex

Abstract:

The recent development of genetically encoded fluorescent neurotransmitter biosensors has opened the door to recording serotonin (5-hydroxytryptamine, 5-HT) signaling dynamics with high temporal and spatial resolution in vivo. While this represents a significant step forward for serotonin research, the utility of available 5-HT biosensors remains to be fully established under diverse in vivo conditions. Here, we used two-photon microscopy in awake mice to examine the effectiveness of specific 5-HT biosensors for monitoring 5-HT dynamics in somatosensory cortex. Initial experiments found that whisker stimulation evoked a striking change in 5-HT biosensor signal. However, similar changes were observed in controls expressing green fluorescent protein, suggesting a potential hemodynamic artifact. Subsequent use of a second control fluorophore with emission peaks separated from the 5-HT biosensor revealed a reproducible, stimulus-locked increase in 5-HT signal. Our data highlight the promise of 5-HT biosensors for in vivo application, provided measurements are carried out with appropriate optical controls.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1021/acschemneuro.3c00725

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
ORCID:
0000-0001-9270-0589
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy and Genetics
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Oxford college:
University College
Role:
Author
ORCID:
0000-0001-7434-9713
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy and Genetics
Oxford college:
Keble College
Role:
Author
ORCID:
0000-0002-2399-0102


More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
204651/Z/16/Z
More from this funder
Funder identifier:
https://ror.org/00k4n6c32
Grant:
953327
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/T033320/1
More from this funder
Funder identifier:
https://ror.org/00cwqg982
Grant:
BB/P003796/1


Publisher:
American Chemical Society
Journal:
ACS Chemical Neuroscience More from this journal
Volume:
15
Issue:
3
Pages:
456-461
Publication date:
2024-01-22
Acceptance date:
2024-01-16
DOI:
ISSN:
1948-7193
Pmid:
38251903


Language:
English
Keywords:
Pubs id:
1604400
Local pid:
pubs:1604400
Deposit date:
2024-10-08
ARK identifier:

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