Natural phasic inhibition of dopamine neurons signals cognitive rigidity.

ABSTRACT: 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undergo phasic inhibition that canonically drives extinction learning-a cognitive-flexibility mechanism for discarding outdated strategies.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 GABA_A-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

SUBMITTER: Burwell SCV 

PROVIDER: S-EPMC11100816 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature