ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The presynaptic choline transporter imposes limits on sustained cortical acetylcholine release and attention.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Trial
- Alterations in hippocampal cholinergic dynamics following CRF infusions into the medial septum of male and female rats.Neurochemistry international · 2024Article
- Article
- Disrupted Choline Clearance and Sustained Acetylcholine ReleaseThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Cholinergic blockade of neuroinflammation: from tissue to RNA regulators.Neuronal signaling · 2022Review
- Cholino-ncRNAs modulate sex-specific- and age-related acetylcholine signals.FEBS letters · 2020Review
- Cholinergic Signaling Dynamics and Cognitive Control of Attention.Current topics in behavioral neurosciences · 2020Review
- Repetitive mild concussion in subjects with a vulnerable cholinergic system: Lasting cholinergic-attentional impairments in CHT+/- mice.Behavioral neuroscience · 2019Article
- Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Electrochemistry at the Synapse.Annual review of analytical chemistry (Palo Alto, Calif.) · 2019Review
- The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models.Behavioral neuroscience · 2018Article
- Hemicholinium-3 sensitive choline transport in human T lymphocytes: Evidence for use as a proxy for brain choline transporter (CHT) capacity.Neurochemistry international · 2017Article
- Article
- Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter.Frontiers in molecular neuroscience · 2017Article
- Cholinergic genetics of visual attention: Human and mouse choline transporter capacity variants influence distractibility.Journal of physiology, Paris · 2016Review
- Differential impact of genetically modulated choline transporter expression on the release of endogenous versus newly synthesized acetylcholine.Neurochemistry international · 2016Article
- The effects of ongoing distraction on the neural processes underlying signal detection.Neuropsychologia · 2016Article
- Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems.Journal of neural transmission (Vienna, Austria : 1996) · 2016Review
- Cortical cholinergic signaling controls the detection of cues.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Functional variation in the gene encoding the presynaptic choline transporter (CHT) has been linked to attention-deficit/hyperactivity disorder. Here, we report that a heterozygous deletion in the CHT gene in mice (CHT(+/-)) limits the capacity of cholinergic neurons to sustain acetylcholine (ACh) release and attentional performance. Cortical microdialysis and amperometric methods revealed that, whereas wild-type and CHT(+/-) animals support equivalent basal ACh release and choline clearance, CHT(+/-) animals exhibit a significant inability to elevate extracellular ACh following basal forebrain stimulation, in parallel with a diminished choline clearance capacity following cessation of stimulation. Consistent with these findings, the density of CHTs in cortical synaptosomal plasma membrane-enriched fractions from unstimulated CHT(+/-) animals matched those observed in wild-type animals despite reductions in CHT levels in total extracts, achieved via a redistribution of CHT from vesicle pools. As a consequence, in CHT(+/-) animals, basal forebrain stimulation was unable to mobilize wild-type quantities of CHT to the plasma membrane. In behavioral studies, CHT(+/-) mice were impaired in performing a sustained attention task known to depend on cortical cholinergic activity. In wild-type mice, but not CHT(+/-) mice, attentional performance increased the density of CHTs in the synaptosomal membrane in the right frontal cortex. Basal CHT levels in vesicle-enriched membranes predicted the degree of CHT mobilization as well as individual variations in performance on the sustained attention task. Our findings demonstrate biochemical and physiological alterations that underlie cognitive impairments associated with genetically imposed reductions in choline uptake capacity.
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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.