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Basal forebrain cholinergic signalling: development, connectivity and roles in cognition

Nature Reviews Neuroscience volume 24, pages 233–251 (2023)Cite this article

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Abstract

Acetylcholine plays an essential role in fundamental aspects of cognition. Studies that have mapped the activity and functional connectivity of cholinergic neurons have shown that the axons of basal forebrain cholinergic neurons innervate the pallium with far more topographical and functional organization than was historically appreciated. Together with the results of studies using new probes that allow release of acetylcholine to be detected with high spatial and temporal resolution, these findings have implicated cholinergic networks in ‘binding’ diverse behaviours that contribute to cognition. Here, we review recent findings on the developmental origins, connectivity and function of cholinergic neurons, and explore the participation of cholinergic signalling in the encoding of cognition-related behaviours.

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Fig. 1: A model for BFCN fate specification.
Fig. 2: Spatial localization and projection patterns of BFCNs.
Fig. 3: Improvements in measurement of in vivo ACh dynamics.

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Acknowledgements

All authors are supported by funds from the NINDS Intramural Research Program.

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Authors and Affiliations

  1. Section on Circuits, Synapses, and Molecular Signalling, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Mala R. Ananth & Lorna W. Role

  2. Section on Genetics of Neuronal Signalling, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Prithviraj Rajebhosale, Ronald Kim & David A. Talmage

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  1. Mala R. Ananth
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Glossary

Chromatin landscape

An umbrella term encompassing chromatin accessibility, long-range contacts and looping, higher-order chromatin structure and DNA/histone modifications.

Collateral projections

Branching neuronal projections from a single neuron targeting multiple brain regions.

Co-release

The release of two (and possibly more) neurotransmitters from the same presynaptic vesicle using the same mechanism.

Co-transmission

The release of multiple neurotransmitters from different presynaptic vesicles via distinct mechanisms but leading to an aggregate effect on synaptic transmission.

En passant release

Neurotransmitter release along axonal projections rather than from an axon terminal.

Fluorescent biosensors

A class of tools used to visualize and measure changes in biological processes using sensitive fluorescence readout in response to a conformational change.

Homeodomain transcription factors

Transcription factors with a conserved helix–turn–helix motif, called a ‘homeodomain’, involved in regulating gene expression early in development.

Morphogens

Secreted signalling molecules that pattern cell and tissue fates during early development.

Neuromodulator

A messenger (including peptides and certain neurotransmitters) that can change the state of a neuron or group of neurons to alter their excitability.

Optogenetics

A technique that uses light to manipulate neuronal activity.

Point-to-point synapses

Synapses at which individual sites of presynaptic release are closely apposed to postsynaptic terminals.

Phasic signalling

Fast, transient signalling in response to the onset of a stimulus.

Radial migration

Migration radially from the ventricular zone towards the directly overlying surface of the brain.

Retrograde signals

Signalling initiated in axon terminals influencing signalling/gene expression in the soma/nucleus.

Single-cell RNA sequencing

Sequencing technology that allows transcriptomic profiling of individual cells/nuclei.

Specification

The process involved in the specification of cell identity.

Synaptic release probability

The likelihood that a neurotransmitter will be released from a presynaptic vesicle.

Tangential migration

Migration parallel to the ventricular zone.

Terminal fields

A collection of axon terminals used to describe innervation of an anatomically defined region.

Theta oscillations

Synchronous neuronal activity between 4 Hz and 8 Hz that corresponds to a behavioural state of alertness and attention in the brain.

Tonic signalling

Slow and graded signalling.

Trophic factors

Peptides (often secreted) that promote growth and survival of cells.

Top-down attention

Intentional and goal-driven attention, as opposed to ‘bottom-up’ attention in response to sensory stimuli.

Valence

The hedonic value (positive or negative) of a stimulus.

Virus-based mapping

The use of viral vectors (anterograde and/or retrograde) to delineate anatomical connections between different brain regions.

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Ananth, M.R., Rajebhosale, P., Kim, R. et al. Basal forebrain cholinergic signalling: development, connectivity and roles in cognition. Nat Rev Neurosci 24, 233–251 (2023). https://doi.org/10.1038/s41583-023-00677-x

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