ReviewThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Forebrain Cholinergic Signaling: Wired and Phasic, Not Tonic, and Causing Behavior.
Review in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed.
- An Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial.JAMA neurology · 2025Trial
- Safety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective MAlzheimer's research & therapy · 2021Trial
- Modulatory effects of α7-nicotinic cholinergic receptors on perceptual sensitivity in a visual signal detection task.Psychopharmacology · 2026Article
- Flexible Multimodal Neural Probe with Integrated Three-Electrode Aptameric Sensing for In Vivo Monitoring of Dopamine Dynamics and Neural Activity.ACS chemical neuroscience · 2026Article
- The subthalamic nucleus-ventral pallidum projection targeting cholinergic circuits modulates chronic pain.PLoS biology · 2026Article
- Falls Induced by Optogenetic Inhibition of Basal Forebrain Cholinergic Projections after Dorsomedial Striatal Dopamine Depletion in a Dual Disruption Model of Falling Vulnerability in Parkinson Disease.bioRxiv : the preprint server for biology · 2026Article
- Spontaneous and stimulus-driven arousal produce distinct acetylcholine dynamics across sensory and prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Reciprocal molecular and cellular cholinergic working memory impairments in Alzheimer's disease model mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Phasic and tonic arousal distinctly shape human decision bias.Communications biology · 2026Article
- Cholinergic Phenotypes of Acetyl-CoA with ATP-Citrate Lyase Link.International journal of molecular sciences · 2026Review
- Layer 6 is a hub for cholinergic modulation in the mouse auditory cortex.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Real-Time In Vivo Monitoring of Cholinergic Neurotransmission in the Mouse Brain Using a Microelectrochemical Choline Biosensor.The European journal of neuroscience · 2025Article
- Cholinergic Dynamics in the Septo-hippocampal System Provide Phasic Multiplexed Signals for Spatial Novelty and Correlate with Behavioral States.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The Central Cholinergic Synapse: A Primer.International journal of molecular sciences · 2025Review
- Cell-type-specific cholinergic control of granular retrosplenial cortex with implications for angular velocity coding across brain states.Progress in neurobiology · 2025Article
- Unique nicotinic responses are present in distinct subtypes of mouse medial prefrontal layer V pyramidal neurons.Scientific reports · 2025Article
- Layer 6 is a hub for cholinergic modulation in the mouse auditory cortex.bioRxiv : the preprint server for biology · 2025Article
- Shared subcortical arousal systems across sensory modalities during transient modulation of attention.NeuroImage · 2025Article
- Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making.Science advances · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Conceptualizations of cholinergic signaling as primarily spatially diffuse and slow-acting are based largely on measures of extracellular brain ACh levels that require several minutes to generate a single data point. In addition, most such studies inhibited the highly potent catalytic enzyme for ACh, AChE, to facilitate measurement of ACh. Absent such inhibition, AChE limits the presence of ambient ACh and thus renders it unlikely that ACh influences target regions via slow changes in extracellular ACh concentrations. We describe an alternative view by which forebrain signaling in cortex driving cognition is largely phasic (milliseconds to perhaps seconds), and unlikely to be volume-transmitted. This alternative is supported by new evidence from real-time amperometric recordings of cholinergic signaling indicating a specific function of rapid, phasic, transient cholinergic signaling in attentional contexts. Previous neurochemical evidence may be reinterpreted in terms of integrated phasic cholinergic activity that mediates specific behavioral and cognitive operations; this reinterpretation fits well with recent computational models. Optogenetic studies support a causal relationship between cholinergic transients and behavior. This occurs in part via transient-evoked muscarinic receptor-mediated high-frequency oscillations in cortical regions. Such oscillations outlast cholinergic transients and thus link transient ACh signaling with more sustained postsynaptic activity patterns to support relatively persistent attentional biases. Reconceptualizing cholinergic function as spatially specific, phasic, and modulating specific cognitive operations is theoretically powerful and may lead to pharmacologic treatments more effective than those based on traditional views.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.