ArticleNature communications2024
VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.
Article in Nature communications, 2024. 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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Who cites it
15 citing papers in PubMed.
- Small-Conductance CaNeuroscience bulletin · 2026Review
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration.Nature communications · 2026Article
- Photostimulation of locus coeruleus CA1 catecholaminergic terminals reversed Spatial memory impairment in an alzheimer's disease mouse model.Psychopharmacology · 2026Article
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Alzheimer's Pathology Enhances Excitatory Synaptic Input and Integration in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Genome-centric metagenomes unveiling microbial functional potential in a glacier river in the Mount everest.World journal of microbiology & biotechnology · 2026Article
- Neuroprotective Effects of Hesperidin and CK2 Inhibitor DRB on AβMolecular neurobiology · 2025Article
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 2025Article
- Tau conveys intrinsic hyperactivity of VTA dopamine neurons but an inability to sustain burst firing.bioRxiv : the preprint server for biology · 2025Article
- Multi-Locus Pro-Dopaminergic Restoration of Reward Brain Circuitry in Reward Deficiency Rescinds Mono-Pharmaceutical Targeting.Neurology (E-Cronicon) · 2025Article
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- Parallel Gene Expression Changes in Ventral Midbrain Dopamine and GABA Neurons during Normal Aging.eNeuro · 2025Article
- Repetitive prefrontal tDCS activates VTA dopaminergic neurons, resulting in attenuation of Alzheimer's Disease-like deficits in Tg2576 mice.Alzheimer's research & therapy · 2025Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.Nature communications · 2024Article
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9 authors.
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Abstract
Alzheimer's disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing in DA neurons caused by reduced activity of small-conductance calcium-activated potassium (SK) channels. RNA sequencing from contents of single patch-clamped DA neurons (Patch-seq) identified up-regulation of the SK channel modulator casein kinase 2 (CK2), which we corroborated by immunohistochemical protein analysis. Pharmacological inhibition of CK2 restored SK channel activity and normal firing patterns in 3xTg-AD mice. These findings identify a mechanism of ion channel dysregulation in VTA DA neurons that could contribute to behavioral abnormalities in AD, paving the way for novel treatment strategies.
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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 Socratic graph.