A specific basal forebrain–medial prefrontal cholinergic pathway improves attentional control in male mice
Scientific Reports. 2026-05-02; :
DOI: 10.1038/s41598-026-51042-8
1. Sci Rep. 2026 May 2. doi: 10.1038/s41598-026-51042-8. Online ahead of print.
A specific basal forebrain-medial prefrontal cholinergic pathway improves
attentional control in male mice.
Fois GR(1), Medrano MC(2), Proville R(3), Caille S(#)(2), Guillem K(#)(4).
Author information:
(1)INSERM U-1084, Université de Poitiers, 86022, Poitiers, France.
(2)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287, Université de Bordeaux,, Bâtiment BBS – 2ème étage, 2, Rue du Dr Hoffmann
Martinot, 33000, Bordeaux, France.
(3)Aquineuro, 33000, Bordeaux, France.
(4)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287, Université de Bordeaux,, Bâtiment BBS – 2ème étage, 2, Rue du Dr Hoffmann
Martinot, 33000, Bordeaux, France. .
(#)Contributed equally
Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is a major
contributor to the balance between attention and inhibitory control, which is
crucial for the execution of adaptive goal-directed behaviors. Yet, our
understanding of the functional heterogeneity within the mPFC, particularly how
distinct cholinergic afferences and circuits regulate these processes, remains
limited. Here, we used in vivo fiber photometry, neuronal tracing, and
chemogenetics manipulations to demonstrate the role of the prelimbic sub-region
of the mPFC (PrL) and its ascending cholinergic projections in a cued-Fixed
Consecutive Number task (FCNcue task) in male mice. We found that following a
transient activation at the initiation of the behavioral response (cue
detection), persistent inhibition of PrL neuronal activity, measured by fiber
photometry, may be necessary to maintain engagement in the task and completion
of the chain of required responses (i.e., optimal responses). Moreover, we found
that the PrL receives dense ACh projections almost exclusively from the most
anterior-medial part of the basal forebrain (BF) comprising the horizontal and
ventral parts of the diagonal band of Broca (HDB and VDB) and the substantia
innominata (SI) nuclei. Finally, chemogenetic activation of this ACh pathway
inhibited PrL activity and enhanced behavioral performance of the mice by
increasing the percentage of optimal responses. Overall, this study provides
insights into the spatial and temporal dynamics of cholinergic signaling to the
PrL and its causal role on attentional control.
© 2026. The Author(s).
DOI: 10.1038/s41598-026-51042-8
PMID: 42067628
Conflict of interest statement: Declarations. Competing interests: The authors
declare no competing interests.