Hippocampal Mossy Fibers Synapses in CA3 Pyramidal Cells Are Altered at an Early Stage in a Mouse Model of Alzheimer's Disease
| العنوان: | Hippocampal Mossy Fibers Synapses in CA3 Pyramidal Cells Are Altered at an Early Stage in a Mouse Model of Alzheimer's Disease |
|---|---|
| المؤلفون: | Virginie F. Labrousse, Silvia Viana da Silva, Noelle Grosjean, Christophe Blanchet, Matthias G. Haberl, Christophe Mulle, Pei Zhang, Andreas Frick |
| المساهمون: | Department of Microbiology and Immunology, Division of Infectious Diseases, Walther Oncology Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2 |
| المصدر: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2019, ⟨10.1523/JNEUROSCI.2868-18.2019⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Mossy fiber (hippocampus), Male, hippocampus, Long-Term Potentiation, Hippocampus, CA3, Neurotransmission, Biology, Hippocampal formation, Synapse, 03 medical and health sciences, Mice, 0302 clinical medicine, Alzheimer Disease, synapse, mossy fiber, Animals, Research Articles, mouse, General Neuroscience, Dentate gyrus, Pyramidal Cells, musculoskeletal, neural, and ocular physiology, Excitatory Postsynaptic Potentials, Long-term potentiation, CA3 Region, Hippocampal, Disease Models, Animal, 030104 developmental biology, nervous system, Synaptic plasticity, Mossy Fibers, Hippocampal, Synapses, Alzheimer, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Early Alzheimer's disease (AD) affects the brain non-uniformly, causing hippocampal memory deficits long before wide-spread brain degeneration becomes evident. Here we addressed whether mossy fiber inputs from the dentate gyrus onto CA3 principal cells are affected in an AD mouse model before amyloid β plaque deposition. We recorded from CA3 pyramidal cells in a slice preparation from 6-month-old male APP/PS1 mice, and studied synaptic properties and intrinsic excitability. In parallel we performed a morphometric analysis of mossy fiber synapses following viral based labeling and 3D-reconstruction. We found that the basal structural and functional properties as well as presynaptic short-term plasticity at mossy fiber synapses are unaltered at 6 months in APP/PS1 mice. However, transient potentiation of synaptic transmission mediated by activity-dependent release of lipids was abolished. Whereas the presynaptic form of mossy fiber long-term potentiation (LTP) was not affected, the postsynaptic LTP of NMDAR-EPSCs was reduced. In addition, we also report an impairment in feedforward inhibition in CA3 pyramidal cells. This study, together with our previous work describing deficits at CA3–CA3 synapses, provides evidence that early AD affects synapses in a projection-dependent manner at the level of a single neuronal population.SIGNIFICANCE STATEMENTBecause loss of episodic memory is considered the cognitive hallmark of Alzheimer's disease (AD), it is important to study whether synaptic circuits involved in the encoding of episodic memory are compromised in AD mouse models. Here we probe alterations in the synaptic connections between the dentate gyrus and CA3, which are thought to be critical for enabling episodic memories to be formed and stored in CA3. We found that forms of synaptic plasticity specific to these synaptic connections are markedly impaired at an early stage in a mouse model of AD, before deposition of β amyloid plaques. Together with previous work describing deficits at CA3–CA3 synapses, we provide evidence that early AD affects synapses in an input-dependent manner within a single neuronal population. |
| اللغة: | English |
| تدمد: | 0270-6474 1529-2401 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c645dfe9953e59af97ca53e78f44d95 https://hal.archives-ouvertes.fr/hal-02418036 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6c645dfe9953e59af97ca53e78f44d95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02706474 15292401 |
|---|