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Published July 11, 2023 | Published + Supplemental Material
Journal Article Open

A functional logic for neurotransmitter corelease in the cholinergic forebrain pathway


The cholinergic system of the basal forebrain plays an integral part in behaviors ranging from attention to learning, partly by altering the impact of noise in neural populations. The circuit computations underlying cholinergic actions are confounded by recent findings that forebrain cholinergic neurons corelease both acetylcholine (ACh) and GABA. We have identified that corelease of ACh and GABA by cholinergic inputs to the claustrum, a structure implicated in the control of attention, has opposing effects on the electrical activity of claustrum neurons that project to cortical vs. subcortical targets. These actions differentially alter neuronal gain and dynamic range in the two types of neurons. In model networks, the differential effects of ACh and GABA toggle network efficiency and the impact of noise on population dynamics between two different projection subcircuits. Such cholinergic switching between subcircuits provides a potential logic for neurotransmitter corelease in implementing behaviorally relevant computations.

Additional Information

© 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). We thank K.L.L Wong, Z. Chia, G. X. Ham, L. Mark, and G. Silberberg for insightful discussions and comments on our paper and K. Chung, S. Kay, R. Tan, P. Teo, Y. C. Teo, and M. Yeow for technical assistance. Supported by the Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 3 (MOE2017-T3-1-002). M.G. was supported by an LKCMedicine LEARN grant (021912-00001), and A.N is supported by the National Science Scholarship awarded by the Agency of Science, Technology and Research, Singapore. Data, Materials, and Software Availability: Software: Code used for analysis and reproduction of IOcurves and the recurrent claustrum network data have been deposited in Github (42, 43). All study data are included in the article and/or SI Appendix. Author contributions: A.N., G.J.A., and M.G. designed research; A.N., Y.Y.T., and M.G. performed research; A.N., Y.Y.T., and M.G. analyzed data; and A.N., G.J.A., and M.G. wrote the paper. The authors declare no competing interest.

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Published - pnas.2218830120.pdf

Supplemental Material - pnas.2218830120.sapp.pdf


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August 22, 2023
October 23, 2023