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Natural phasic inhibition of dopamine neurons signals cognitive rigidity.

Publication ,  Journal Article
Burwell, SCV; Yan, H; Lim, SSX; Shields, BC; Tadross, MR
Published in: bioRxiv
July 13, 2024

When animals unexpectedly fail, their dopamine neurons undergo phasic inhibition that canonically drives extinction learning-a cognitive-flexibility mechanism for discarding outdated strategies. However, the existing evidence equates natural and artificial phasic inhibition, despite their spatiotemporal differences. Addressing this gap, we targeted a GABAA-receptor antagonist precisely to dopamine neurons, yielding three unexpected findings. First, this intervention blocked natural phasic inhibition selectively, leaving tonic activity unaffected. Second, blocking natural phasic inhibition accelerated extinction learning-opposite to canonical mechanisms. Third, our approach selectively benefitted perseverative mice, restoring rapid extinction without affecting new reward learning. Our findings reveal that extinction learning is rapid by default and slowed by natural phasic inhibition-challenging foundational learning theories, while delineating a synaptic mechanism and therapeutic target for cognitive rigidity.

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Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

July 13, 2024

Location

United States
 

Citation

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Burwell, S. C. V., Yan, H., Lim, S. S. X., Shields, B. C., & Tadross, M. R. (2024). Natural phasic inhibition of dopamine neurons signals cognitive rigidity. BioRxiv. https://doi.org/10.1101/2024.05.09.593320
Burwell, Sasha C. V., Haidun Yan, Shaun S. X. Lim, Brenda C. Shields, and Michael R. Tadross. “Natural phasic inhibition of dopamine neurons signals cognitive rigidity.BioRxiv, July 13, 2024. https://doi.org/10.1101/2024.05.09.593320.
Burwell SCV, Yan H, Lim SSX, Shields BC, Tadross MR. Natural phasic inhibition of dopamine neurons signals cognitive rigidity. bioRxiv. 2024 Jul 13;
Burwell, Sasha C. V., et al. “Natural phasic inhibition of dopamine neurons signals cognitive rigidity.BioRxiv, July 2024. Pubmed, doi:10.1101/2024.05.09.593320.
Burwell SCV, Yan H, Lim SSX, Shields BC, Tadross MR. Natural phasic inhibition of dopamine neurons signals cognitive rigidity. bioRxiv. 2024 Jul 13;

Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

July 13, 2024

Location

United States