ArticleMolecular neurodegeneration2023
Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Exercise and neural circuit stability in early Alzheimer's disease: evidence across memory, executive, cholinergic, and circadian systems.Frontiers in aging neuroscience · 2026Review
- Microglia-Neuron Interactions in Alzheimer's Disease.Current neuropharmacology · 2026Review
- Time-dependent histological characterization of amyloid-β induced cholinergic and glial alterations and their modulation by dehydroepiandrosterone sulfate (DHEAS).Frontiers in endocrinology · 2026Article
- The medial septum-hippocampus-lateral septum circuitry in spatial memory: linking healthy function to early Alzheimer's disease and translational opportunities.Translational neurodegeneration · 2025Review
- Improving vulnerable Calbindin1Translational neurodegeneration · 2025Article
- Haloperidol-Induced Catalepsy and Its Correlations with Acetylcholinesterase Activity in Different Brain Structures of Mice.Neurology international · 2024Article
- Exercise-conditioned plasma ameliorates postoperative cognitive dysfunction by activating hippocampal cholinergic circuit and enhancing BDNF/TrkB signaling.Cell communication and signaling : CCS · 2024Article
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Authors and funding
24 authors at 6 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAbnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer's disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive.
methodsTo investigate the effect and mechanism of the cholinergic circuit in Alzheimer's disease-related hippocampal memory, overexpression of human wild-type Tau (hTau) in medial septum (MS)-hippocampus (HP) cholinergic was achieved by specifically injecting pAAV-EF1α-DIO-hTau-eGFP virus into the MS of ChAT-Cre mice. Immunostaining, behavioral analysis and optogenetic activation experiments were used to detect the effect of hTau accumulation on cholinergic neurons and the MS-CA1 cholinergic circuit. Patch-clamp recordings and in vivo local field potential recordings were used to analyze the influence of hTau on the electrical signals of cholinergic neurons and the activity of cholinergic neural circuit networks. Optogenetic activation combined with cholinergic receptor blocker was used to detect the role of cholinergic receptors in spatial memory.
resultsIn the present study, we found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. In addition to an inhibitory effect on neuronal excitability, theta synchronization between the MS and CA1 subsets was significantly disrupted during memory consolidation after overexpressing hTau in the MS. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm-dependent manner.
conclusionsOur study not only reveals the vulnerability of a novel MS-CA1 cholinergic circuit to AD-like tau accumulation but also provides a rhythm- and time window-dependent strategy to target the MS-CA1 cholinergic circuit, thereby rescuing tau-induced spatial cognitive functions.
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