| |  Online-Ressource |
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| Verfasst von: | Mehr, Annika [VerfasserIn]  |
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| | Hick, Meike [VerfasserIn] |
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| | Ludewig, Susann [VerfasserIn] |
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| | Müller, Michaela [VerfasserIn] |
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| | Herrmann, Ulrike [VerfasserIn] |
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| | Engelhardt, Jakob von [VerfasserIn] |
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| | Wolfer, David P. [VerfasserIn] |
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| | Korte, Martin [VerfasserIn] |
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| | Müller, Ulrike C. [VerfasserIn] |
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| Titel: | Lack of APP and APLP2 in GABAergic forebrain neurons impairs synaptic plasticity and cognition |
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| Verf.angabe: | Annika Mehr, Meike Hick, Susann Ludewig, Michaela Müller, Ulrike Herrmann, Jakob von Engelhardt, David P. Wolfer, Martin Korte and Ulrike C. Müller |
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| E-Jahr: | 2020 |
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| Jahr: | 26 March 2020 |
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| Umfang: | 20 S. |
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| Fussnoten: | Gesehen am 11.12.2020 |
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| Titel Quelle: | Enthalten in: Cerebral cortex |
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| Ort Quelle: | Oxford : Oxford Univ. Press, 1991 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 30(2020), 7, Seite 4044-4063 |
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| ISSN Quelle: | 1460-2199 |
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| Abstract: | Amyloid-ss precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, yet its physiological functions remain incompletely understood. Previous studies had indicated important synaptic functions of APP and the closely related homologue APLP2 in excitatory forebrain neurons for spine density, synaptic plasticity, and behavior. Here, we show that APP is also widely expressed in several interneuron subtypes, both in hippocampus and cortex. To address the functional role of APP in inhibitory neurons, we generated mice with a conditional APP/APLP2 double knockout (cDKO) in GABAergic forebrain neurons using DlxCre mice. These DlxCre cDKO mice exhibit cognitive deficits in hippocampus-dependent spatial learning and memory tasks, as well as impairments in species-typic nesting and burrowing behaviors. Deficits at the behavioral level were associated with altered neuronal morphology and synaptic plasticity Long-Term Potentiation (LTP). Impaired basal synaptic transmission at the Schafer collateral/CA1 pathway, which was associated with altered compound excitatory/inhibitory synaptic currents and reduced action potential firing of CA1 pyramidal cells, points to a disrupted excitation/inhibition balance in DlxCre cDKOs. Together, these impairments may lead to hippocampal dysfunction. Collectively, our data reveal a crucial role of APP family proteins in inhibitory interneurons to maintain functional network activity. |
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| DOI: | doi:10.1093/cercor/bhaa025 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1093/cercor/bhaa025 |
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| | DOI: https://doi.org/10.1093/cercor/bhaa025 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | alzheimers-disease |
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| | amyloid precursor protein |
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| | behavior |
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| | deficits |
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| | dendritic spines |
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| | excitation/inhibition balance |
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| | expression |
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| | generation |
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| | hippocampal neuron |
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| | interneurons |
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| | long-term potentiation |
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| | mice lacking |
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| | morphology |
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| | synaptic plasticity |
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| K10plus-PPN: | 1742606652 |
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| Verknüpfungen: | → Zeitschrift |
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Lack of APP and APLP2 in GABAergic forebrain neurons impairs synaptic plasticity and cognition / Mehr, Annika [VerfasserIn]; 26 March 2020 (Online-Ressource)
