The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding
Summary: There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenes...
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Elsevier
2019-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719311659 |
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doaj-90855fdcacba470a93f8234bea3604cb2020-11-25T01:38:27ZengElsevierCell Reports2211-12472019-10-01292317331.e5The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory EncodingPaula A. Pousinha0Xavier Mouska1Daniela Bianchi2Mariana Temido-Ferreira3Joana Rajão-Saraiva4Rui Gomes5Sebastian P. Fernandez6Ana Rita Salgueiro-Pereira7Carine Gandin8Elisabeth F. Raymond9Jacques Barik10Romain Goutagny11Ingrid Bethus12Luisa V. Lopes13Michele Migliore14Hélène Marie15Université Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, France; Corresponding authorUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceInstitute of Biophysics, National Research Council, Palermo, ItalyInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa, PortugalInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa, PortugalUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceUniversité de Strasbourg, CNRS UMR 7364, LNCA, Strasbourg, FranceUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceInstituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisboa, PortugalInstitute of Biophysics, National Research Council, Palermo, ItalyUniversité Côte d’Azur, CNRS UMR 7275, IPMC, Valbonne, FranceSummary: There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenesis, and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothesize that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological, and behavioral techniques, we show that pathological AICD levels weaken CA1 neuron firing activity through a gene-transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the γ-frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal aging to AD. : Pousinha et al. report that increased AICD levels, a peptide representing amyloid precursor protein (APP) C-terminal domain, render CA1 pyramidal neurons hypoexcitable by altering Ca+ and K+ channel conductances. Modeling this alteration predicts decreased gamma oscillations. They show that increasing AICD levels in vivo weakens gamma-oscillation-dependent spatial memory. Keywords: AICD, APP, Alzheimer’s disease, neuron firing, brain oscillations, memory encodinghttp://www.sciencedirect.com/science/article/pii/S2211124719311659 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Paula A. Pousinha Xavier Mouska Daniela Bianchi Mariana Temido-Ferreira Joana Rajão-Saraiva Rui Gomes Sebastian P. Fernandez Ana Rita Salgueiro-Pereira Carine Gandin Elisabeth F. Raymond Jacques Barik Romain Goutagny Ingrid Bethus Luisa V. Lopes Michele Migliore Hélène Marie |
| spellingShingle |
Paula A. Pousinha Xavier Mouska Daniela Bianchi Mariana Temido-Ferreira Joana Rajão-Saraiva Rui Gomes Sebastian P. Fernandez Ana Rita Salgueiro-Pereira Carine Gandin Elisabeth F. Raymond Jacques Barik Romain Goutagny Ingrid Bethus Luisa V. Lopes Michele Migliore Hélène Marie The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding Cell Reports |
| author_facet |
Paula A. Pousinha Xavier Mouska Daniela Bianchi Mariana Temido-Ferreira Joana Rajão-Saraiva Rui Gomes Sebastian P. Fernandez Ana Rita Salgueiro-Pereira Carine Gandin Elisabeth F. Raymond Jacques Barik Romain Goutagny Ingrid Bethus Luisa V. Lopes Michele Migliore Hélène Marie |
| author_sort |
Paula A. Pousinha |
| title |
The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding |
| title_short |
The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding |
| title_full |
The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding |
| title_fullStr |
The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding |
| title_full_unstemmed |
The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding |
| title_sort |
amyloid precursor protein c-terminal domain alters ca1 neuron firing, modifying hippocampus oscillations and impairing spatial memory encoding |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2019-10-01 |
| description |
Summary: There is a growing consensus that Alzheimer's disease (AD) involves failure of the homeostatic machinery, which underlies the firing stability of neural circuits. What are the culprits leading to neuron firing instability? The amyloid precursor protein (APP) is central to AD pathogenesis, and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothesize that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological, and behavioral techniques, we show that pathological AICD levels weaken CA1 neuron firing activity through a gene-transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the γ-frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal aging to AD. : Pousinha et al. report that increased AICD levels, a peptide representing amyloid precursor protein (APP) C-terminal domain, render CA1 pyramidal neurons hypoexcitable by altering Ca+ and K+ channel conductances. Modeling this alteration predicts decreased gamma oscillations. They show that increasing AICD levels in vivo weakens gamma-oscillation-dependent spatial memory. Keywords: AICD, APP, Alzheimer’s disease, neuron firing, brain oscillations, memory encoding |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719311659 |
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