Hippocampal hyperactivity in a rat model of Alzheimer's disease
| Autor: | A. Claudio Cuello, Igor Klyubin, Niklas Henneberg, Hans-Rüdiger Geis, Falko Fuhrmann, Kevin Keppler, Stefan Remy, Kerstin Hoffmann, Detlef Friedrichs, Daniel Justus, Julia Steffen, Yingjie Qi, Martin Fuhrmann, Liudmila Sosulina, Manuel Mittag, Michael J. Rowan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
physiology [Excitatory Postsynaptic Potentials] Amyloid beta Transgene Hippocampus hyperexcitability Alzheimer's disease disease model β-amyloidosis metabolism [Hippocampus] Biology Hippocampal formation Inhibitory postsynaptic potential Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience Amyloid beta-Protein Precursor pathology [Alzheimer Disease] 0302 clinical medicine Organ Culture Techniques In vivo Alzheimer Disease metabolism [Amyloid beta-Protein Precursor] medicine Extracellular Biological neural network Animals ddc:610 030304 developmental biology 0303 health sciences Chemistry Excitatory Postsynaptic Potentials medicine.disease Rats Disease Models Animal pathology [Hippocampus] nervous system genetics [Amyloid beta-Protein Precursor] biology.protein Female Rats Transgenic Neuroscience 030217 neurology & neurosurgery metabolism [Alzheimer Disease] |
| Zdroj: | Journal of neurochemistry 157(6), 2128-2144 (2021). doi:10.1111/jnc.15323 Journal of neurochemistry, 157(6):2128-2144 Journal of Neurochemistry |
| DOI: | 10.1111/jnc.15323 |
| Popis: | Neuronal network dysfunction is a hallmark of Alzheimer’s disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in a rat model of AD at an early disease stage at the beginning of extracellular amyloid beta (Aβ) deposition. We established two-photon Ca2+-imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slices in vitro revealed changes in the passive properties and intrinsic excitability of CA1 pyramidal neurons. Furthermore, we observed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. Surprisingly, all parameters measured to quantify synaptic inhibition and excitation onto CA1 pyramidal neurons were intact suggesting a cell immanent deficit. Our data support the view that altered intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of disease progression. |
| Databáze: | OpenAIRE |
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