Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control
Abstract This study investigates how norepinephrine (NE) and acetylcholine (ACh) in the prefrontal cortex (PFC) modulate inhibitory control, a critical executive function. Using fluorescent sensors, we tracked prefrontal NE/ACh dynamics in mice during inhibitory control tasks and found strong NE-ACh...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62317-5 |
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| author | Yuxiang Andy Liu Yuhan Nong Jiesi Feng Guochuan Li Paul Sajda Yulong Li Qi Wang |
| author_facet | Yuxiang Andy Liu Yuhan Nong Jiesi Feng Guochuan Li Paul Sajda Yulong Li Qi Wang |
| author_sort | Yuxiang Andy Liu |
| collection | DOAJ |
| description | Abstract This study investigates how norepinephrine (NE) and acetylcholine (ACh) in the prefrontal cortex (PFC) modulate inhibitory control, a critical executive function. Using fluorescent sensors, we tracked prefrontal NE/ACh dynamics in mice during inhibitory control tasks and found strong NE-ACh coherence at 0.4–0.8 Hz. Inhibiting locus coeruleus (LC) neurons projecting to the basal forebrain (BF) induced greater impairments in inhibitory control than targeting those projecting to the PFC, despite partial overlap. This inhibition disrupted NE-ACh phase synchrony between successful and failed trials, indicating its importance. Conversely, silencing cholinergic neurons projecting to the LC did not affect task performance or phase synchrony. Neuropixels recordings revealed that disrupting LC-BF projections impaired PFC neuronal encoding and altered population firing patterns linked to inhibitory control. These findings suggest that the LC and cholinergic systems jointly modulate inhibitory control by influencing NE-ACh synchrony and its effect on PFC activity, underscoring their role in cognitive control. |
| format | Article |
| id | doaj-art-ba4410f7446a4193bcf4073e6dfc2798 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ba4410f7446a4193bcf4073e6dfc27982025-08-20T03:46:17ZengNature PortfolioNature Communications2041-17232025-08-0116112110.1038/s41467-025-62317-5Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory controlYuxiang Andy Liu0Yuhan Nong1Jiesi Feng2Guochuan Li3Paul Sajda4Yulong Li5Qi Wang6Department of Biomedical Engineering, Columbia University, ET 351, 500 W 120th StDepartment of Biomedical Engineering, Columbia University, ET 351, 500 W 120th StState Key Laboratory of Membrane Biology, School of Life Sciences, Peking UniversityState Key Laboratory of Membrane Biology, School of Life Sciences, Peking UniversityDepartment of Biomedical Engineering, Columbia University, ET 351, 500 W 120th StState Key Laboratory of Membrane Biology, School of Life Sciences, Peking UniversityDepartment of Biomedical Engineering, Columbia University, ET 351, 500 W 120th StAbstract This study investigates how norepinephrine (NE) and acetylcholine (ACh) in the prefrontal cortex (PFC) modulate inhibitory control, a critical executive function. Using fluorescent sensors, we tracked prefrontal NE/ACh dynamics in mice during inhibitory control tasks and found strong NE-ACh coherence at 0.4–0.8 Hz. Inhibiting locus coeruleus (LC) neurons projecting to the basal forebrain (BF) induced greater impairments in inhibitory control than targeting those projecting to the PFC, despite partial overlap. This inhibition disrupted NE-ACh phase synchrony between successful and failed trials, indicating its importance. Conversely, silencing cholinergic neurons projecting to the LC did not affect task performance or phase synchrony. Neuropixels recordings revealed that disrupting LC-BF projections impaired PFC neuronal encoding and altered population firing patterns linked to inhibitory control. These findings suggest that the LC and cholinergic systems jointly modulate inhibitory control by influencing NE-ACh synchrony and its effect on PFC activity, underscoring their role in cognitive control.https://doi.org/10.1038/s41467-025-62317-5 |
| spellingShingle | Yuxiang Andy Liu Yuhan Nong Jiesi Feng Guochuan Li Paul Sajda Yulong Li Qi Wang Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control Nature Communications |
| title | Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| title_full | Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| title_fullStr | Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| title_full_unstemmed | Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| title_short | Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| title_sort | phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control |
| url | https://doi.org/10.1038/s41467-025-62317-5 |
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