ArticleProceedings of the National Academy of Sciences of the United States of America2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 2 of them syntheses that pooled it.
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Who cites it
112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- Varenicline for cognitive impairment in people with schizophrenia: systematic review and meta-analysis.Psychopharmacology · 2020Pooled it
- Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies.Progress in neuro-psychopharmacology & biological psychiatry · 2017Pooled it
- Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia: Randomized Trial with an Extended-Release Formulation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Pharmacological Manipulation of Cortical Inhibition in the Dorsolateral Prefrontal Cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- The prefrontal cortex across scales: laminar architecture, white-matter constraints, and distributed control in cognition.Brain structure & function · 2026Review
- Nicotine causes highly localized and tuned changes in thalamocortical gain that cascade strongly and selectively through the cortical circuit.bioRxiv : the preprint server for biology · 2026Article
- Astrocytes mediate the pro-cognitive value of α7nAChRs and of α7nAChR-targeting therapeutics.bioRxiv : the preprint server for biology · 2026Article
- Kynurenic acid signaling expands in human and nonhuman primates and impairs dorsolateral prefrontal cortical cognition that is key to mental illness.Molecular psychiatry · 2026Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Targeting Neuronal Alpha7 Nicotinic Acetylcholine Receptor Upregulation in Age-Related Neurological Disorders.Cellular and molecular neurobiology · 2025Review
- Unique nicotinic responses are present in distinct subtypes of mouse medial prefrontal layer V pyramidal neurons.Scientific reports · 2025Article
- Therapeutic Targeting of the α7 Nicotinic Receptor: Challenges and Prospects for Cognitive Improvement in Alzheimer's and Schizophrenia.Basic & clinical pharmacology & toxicology · 2025Review
- The Effects of Air Pollution on Neurological Diseases: A Narrative Review on Causes and Mechanisms.Toxics · 2025Review
- Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.Biological psychiatry · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.Current neuropharmacology · 2025Review
- A novel multimodal pharmacologic approach using guanfacine, N-acetylcysteine, and donepezil in severe TBI: a case series.Frontiers in rehabilitation sciences · 2025Article
- Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in α7 nicotinic acetylcholine receptors (α7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011) Nat Neurosci 14(12):1510-1512]; however, little is known about how α7-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995) Neuron 14(3):477-485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore α7-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of α7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008) Nature 454(7208):1110-1114]. We additionally show that α7-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to α7-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia.
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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.