ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Impaired Cholinergic Excitation of Prefrontal Attention Circuitry in the TgCRND8 Model of Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 30 citations in OpenAlex.
- Cholinergic modulation of hippocampal CA1 pyramidal cell excitability in ArxExperimental neurology · 2026Article
- Mechanism of SK2 channel gating and its modulation by the bee toxin apamin and small molecules.eLife · 2025Article
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- HIV-1 Tat protein alters medial prefrontal cortex neuronal activity and recognition memory.iScience · 2025Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.Nature communications · 2024Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.bioRxiv : the preprint server for biology · 2023Article
- Selective impairment of circuits between prefrontal cortex glutamatergic neurons and basal forebrain cholinergic neurons in a tauopathy mouse model.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies.Brain : a journal of neurology · 2022Article
- Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer's disease.Nature communications · 2022Article
- SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Review
- CRISPR/Cas9-Correctable mutation-related molecular and physiological phenotypes in iPSC-derived Alzheimer's PSEN2Acta neuropathologica communications · 2017Article
- AmyloidInternational journal of peptides · 2017Article
- Corticothalamic network dysfunction and behavioral deficits in a mouse model of Alzheimer's disease.Neurobiology of aging · 2016Article
- Article
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Authors and funding
4 authors at 4 institutions in 4 countries.
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Abstract
Attention deficits in Alzheimer's disease can exacerbate its other cognitive symptoms, yet relevant disruptions of key prefrontal circuitry are not well understood. Here, in the TgCRND8 mouse model of this neurological disorder, we demonstrate and characterize a disruption of cholinergic excitation in the major corticothalamic layer of the prefrontal cortex, in which modulation by acetylcholine is essential for optimal attentional function. Using electrophysiology with concurrent multiphoton imaging, we show that layer 6 pyramidal cells are unable to sustain cholinergic excitation to the same extent as their nontransgenic littermate controls, as a result of the excessive activation of calcium-activated hyperpolarizing conductances. We report that cholinergic excitation can be improved in TgCRND8 cortex by pharmacological blockade of SK channels, suggesting a novel target for the treatment of cognitive dysfunction in Alzheimer's disease. SIGNIFICANCE STATEMENT: Alzheimer's disease is accompanied by attention deficits that exacerbate its other cognitive symptoms. In brain slices of a mouse model of this neurological disorder, we demonstrate, characterize, and rescue impaired cholinergic excitation of neurons essential for optimal attentional performance. In particular, we show that the excessive activation of a calcium-activated potassium conductance disrupts the acetylcholine excitation of prefrontal layer 6 pyramidal neurons and that its blockade normalizes responses. These findings point to a novel potential target for the treatment of cognitive dysfunction in Alzheimer's disease.
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