Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis
In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-<i>β</i> (A<i>β</i>) peptides have been shown to play a...
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MDPI AG
2020-07-01
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| author | Jennifer Mayordomo-Cava Guillermo Iborra-Lázaro Souhail Djebari Sara Temprano-Carazo Irene Sánchez-Rodríguez Danko Jeremic Agnès Gruart José María Delgado-García Lydia Jiménez-Díaz Juan D. Navarro-López |
| author_facet | Jennifer Mayordomo-Cava Guillermo Iborra-Lázaro Souhail Djebari Sara Temprano-Carazo Irene Sánchez-Rodríguez Danko Jeremic Agnès Gruart José María Delgado-García Lydia Jiménez-Díaz Juan D. Navarro-López |
| author_sort | Jennifer Mayordomo-Cava |
| collection | DOAJ |
| description | In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-<i>β</i> (A<i>β</i>) peptides have been shown to play a causal role. Among different A<i>β</i> species, A<i>β</i><sub>25–35</sub> has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble A<i>β</i> forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of A<i>β</i><sub>25–35</sub> we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to <i>Schaffer</i> collaterals. A<i>β</i><sub>25–35</sub> was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in A<i>β</i><sub>25–35</sub> amyloidosis model. |
| first_indexed | 2024-03-10T18:20:32Z |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T18:20:32Z |
| publishDate | 2020-07-01 |
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| spelling | doaj.art-174c6b960dbe4a30beb5ed0eb14ab7032023-11-20T07:20:51ZengMDPI AGBiology2079-77372020-07-019717510.3390/biology9070175Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of AmyloidosisJennifer Mayordomo-Cava0Guillermo Iborra-Lázaro1Souhail Djebari2Sara Temprano-Carazo3Irene Sánchez-Rodríguez4Danko Jeremic5Agnès Gruart6José María Delgado-García7Lydia Jiménez-Díaz8Juan D. Navarro-López9Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainDivision of Neurosciences, Pablo de Olavide University, 41013 Seville, SpainDivision of Neurosciences, Pablo de Olavide University, 41013 Seville, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainNeurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, SpainIn early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-<i>β</i> (A<i>β</i>) peptides have been shown to play a causal role. Among different A<i>β</i> species, A<i>β</i><sub>25–35</sub> has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble A<i>β</i> forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of A<i>β</i><sub>25–35</sub> we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to <i>Schaffer</i> collaterals. A<i>β</i><sub>25–35</sub> was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in A<i>β</i><sub>25–35</sub> amyloidosis model.https://www.mdpi.com/2079-7737/9/7/175Alzheimer modelamyloid-<i>β</i>hippocampusin vivosynaptic plasticitymetaplasticity |
| spellingShingle | Jennifer Mayordomo-Cava Guillermo Iborra-Lázaro Souhail Djebari Sara Temprano-Carazo Irene Sánchez-Rodríguez Danko Jeremic Agnès Gruart José María Delgado-García Lydia Jiménez-Díaz Juan D. Navarro-López Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis Biology Alzheimer model amyloid-<i>β</i> hippocampus in vivo synaptic plasticity metaplasticity |
| title | Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis |
| title_full | Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis |
| title_fullStr | Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis |
| title_full_unstemmed | Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis |
| title_short | Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis |
| title_sort | impairments of synaptic plasticity induction threshold and network oscillatory activity in the hippocampus underlie memory deficits in a non transgenic mouse model of amyloidosis |
| topic | Alzheimer model amyloid-<i>β</i> hippocampus in vivo synaptic plasticity metaplasticity |
| url | https://www.mdpi.com/2079-7737/9/7/175 |
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