Unlocking opioid neuropeptide dynamics with genetically encoded biosensors.
Nat Neurosci
; 27(9): 1844-1857, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39009835
ABSTRACT
Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biosensing Techniques
/
Optogenetics
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: