ArticleFrontiers in neural circuits2017
Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.
Article in Frontiers in neural circuits, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Pharmacological Manipulations of Physiological Arousal and Sleep-Like Slow Waves Modulate Sustained Attention.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Trial
- Synaptic Interactions Between Serotonergic and Dopaminergic Systems in Parkinson's Disease.Current neuropharmacology · 2025Review
- Long lasting effects of perinatal exposure to the Chlorpyrifos pesticide on sleep, breathing, and neuroinflammation in adult mice.PloS one · 2025Article
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.Molecular psychiatry · 2024Article
- Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Article
- Associations of acetylcholinesterase inhibition between pesticide spray seasons with depression and anxiety symptoms in adolescents, and the role of sex and adrenal hormones on gender moderation.Exposure and health · 2021Article
- Article
- Cortical ChATeLife · 2020Article
- The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain.International journal of molecular sciences · 2020Review
- Targeted neurotransmitter metabolomics profiling of oleanolic acid in the treatment of spontaneously hypertensive rats.RSC advances · 2019Article
- Cellular, Synaptic and Network Effects of Acetylcholine in the Neocortex.Frontiers in neural circuits · 2019Review
- Visual Attention Deficits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex.Computational psychiatry (Cambridge, Mass.) · 2018Article
- Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
- Ready, set, go: the bridging of attention to action by acetylcholine in prefrontal cortex.The Journal of physiology · 2018Article
- It's Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish.Frontiers in behavioral neuroscience · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.
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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.