ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Heightened Hippocampal β-Adrenergic Receptor Function Drives Synaptic Potentiation and Supports Learning and Memory in the TgF344-AD Rat Model during Prodromal Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Daily biofeedback to modulate heart rate oscillations affects structural volume in hippocampal subregions targeted by the locus coeruleus in older adults but not younger adults.Neurobiology of aging · 2023Trial
- Neuroinflammation and noradrenergic modulation with β2-adrenoceptors: Emerging therapeutic targets for Parkinson's diseases.Neural regeneration research · 2026Article
- A new hope: locus coeruleus-norepinephrine system at the nexus of neuropsychiatric symptoms.Molecular psychiatry · 2026Review
- Excitatory cholecystokinin neurons in the CA3 area regulate the navigation learning and neuroplasticity.eLife · 2026Article
- Neuroprotective properties ofIBRO neuroscience reports · 2026Article
- Vulnerability of the locus coeruleus-entorhinal cortex white matter tract in autosomal dominant Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Fear extinction induces maladaptive generalization via noradrenergic and GABAergic systems.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spatial pattern separation deficits in early Alzheimer's disease are comparable in humans and animal models.Scientific reports · 2026Article
- Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.bioRxiv : the preprint server for biology · 2025Article
- Activation of Locus Coeruleus-Hippocampus Tyrosine Hydroxylase Projection Contributes to the Surgical Incision Pain-Induced Memory Consolidation Enhancement in Mice.CNS neuroscience & therapeutics · 2025Article
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Article
- Partial normalization of hippocampal oscillatory activity during sleep in TgF344-AD rats coincides with increased cholinergic synapses at early-plaque stage of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Insights From TgF344-AD, a Double Transgenic Rat Model in Alzheimer's Disease Research.Physiological research · 2025Review
- Deciphering the Role of Adrenergic Receptors in Alzheimer's Disease: Paving the Way for Innovative Therapies.Biomolecules · 2025Review
- Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Pharmacologically increasing O-GlcNAcylation increases complexity of astrocytes in the dentate gyrus of TgF344-AD rats.Frontiers in aging neuroscience · 2025Article
- Factors Affecting Resilience and Prevention of Alzheimer's Disease and Related Dementias.Annals of neurology · 2024Review
- In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat.Brain, behavior, & immunity - health · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The central noradrenergic (NA) system is critical for the maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer's disease (AD). In fact, the locus coeruleus (LC), the sole source of norepinephrine (NE) for >90% of the brain, is the first site of pathologic tau accumulation in human AD with axon loss throughout forebrain, including hippocampus. The dentate gyrus is heavily innervated by LC-NA axons, where released NE acts on β-adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex to facilitate long-term synaptic plasticity and memory formation. These synapses experience dysfunction in early AD before cognitive impairment. In the TgF344-AD rat model of AD, degeneration of LC-NA axons in hippocampus recapitulates human AD, providing a preclinical model to investigate synaptic and behavioral consequences. Using immunohistochemistry, Western blot analysis, and brain slice electrophysiology in 6- to 9-month-old wild-type and TgF344-AD rats, we discovered that the loss of LC-NA axons coincides with the heightened β-AR function at medial perforant path-dentate granule cell synapses that is responsible for the increase in LTP magnitude at these synapses. Furthermore, novel object recognition is facilitated in TgF344-AD rats that requires β-ARs, and pharmacological blockade of β-ARs unmasks a deficit in extinction learning only in TgF344-AD rats, indicating a greater reliance on β-ARs in both behaviors. Thus, a compensatory increase in β-AR function during prodromal AD in TgF344-AD rats heightens synaptic plasticity and preserves some forms of learning and memory.
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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.