A5024522246- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Memory and Neural Mechanisms
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- Neural dynamics and brain function
- Ion channel regulation and function
- Genetics, Bioinformatics, and Biomedical Research
- Monoclonal and Polyclonal Antibodies Research
- Machine Learning in Bioinformatics
- Protein Structure and Dynamics
- Resilience and Mental Health
- Receptor Mechanisms and Signaling
- Childhood Cancer Survivors' Quality of Life
- Cellular transport and secretion
Amsterdam Neuroscience
2019-2025
Royal Netherlands Academy of Arts and Sciences
2013-2025
Netherlands Institute for Neuroscience
2014-2025
University of Amsterdam
2019-2025
Institute of Life Sciences
2025
University of California, San Diego
2009-2021
Northwestern University
2017
American Academy of Arts and Sciences
2014
Royal Academy of Art
2013
The Netherlands Cancer Institute
2000-2010
NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well depression (LTD) of synaptic transmission, cellular models learning and memory. A long-standing view proposes that a high level Ca 2+ entry through NMDARs triggers LTP; lower LTD. Here we show ligand binding to is sufficient induce LTD; neither ion flow nor rise required. However, basal levels are permissively Lowering, but not maintaining, with chelators blocks LTD drives strong potentiation, indicating control...
Abstract Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience evolved into a widely debated concept. External factors such stimulation associated with AD, but exact cellular molecular underpinnings not completely understood. In this review, we discuss current definitions used in field, highlight translational...
Long-term potentiation (LTP), a cellular model of learning and memory, produces both an enhancement synaptic function increase in the size associated dendritic spine. Synaptic insertion AMPA receptors is known to play important role mediating strength during LTP, whereas receptor trafficking structural changes remains unexplored. Here, we examine how cell maintains correlation between spine synapse LTP. We found that cells exploit elegant solution by linking processes single molecule:...
The mechanisms by which β-amyloid (Aβ), a peptide fragment believed to contribute Alzheimer’s disease, leads synaptic deficits are not known. Here we find that elevated oligomeric Aβ requires ion flux-independent function of NMDA receptors (NMDARs) produce depression. activates this metabotropic NMDAR on GluN2B-containing NMDARs but those containing GluN2A. Furthermore, selective loss GluN2B responses, effecting switch in subunit composition from GluN2A, process normally observed during...
The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent strengthening, its hippocampus-dependent remains elusive. By combining viral-mediated vivo gene with vitro patch-clamp recordings, we found that the inhibitory avoidance task, contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses dorsal hippocampus. To block endogenous AMPARs, expressed...
Significance In Alzheimer’s disease, soluble clusters of amyloid-β (Aβ) are believed to degrade synapses and impair memory formation. The removal AMPA receptors from was previously shown be a critical step in Aβ-driven synapse loss. this report, we establish that contain subunit GluA3 play central role synaptic deficits. Neurons lack resistant weakening inhibition plasticity, mice were impairment premature mortality. Our experiments suggest Aβ initiates deficits by removing GluA3-containing synapses.
Beta-amyloid (Aβ) depresses excitatory synapses by a poorly understood mechanism requiring NMDA receptor (NMDAR) function. Here, we show that increased PSD-95, major synaptic scaffolding molecule, blocks the effects of Aβ on synapses. The protective effect persists in tissue lacking AMPA subunit GluA1, which prevents confounding potentiation PSD-95. modifies conformation NMDAR C-terminal domain (CTD) and its interaction with protein phosphatase 1 (PP1), producing weakening. Higher endogenous...
The reproducibility crisis (or replication crisis) in biomedical research is a particularly existential and under-addressed issue the field of behavioral neuroscience, where, spite efforts to standardize testing assay protocols, several known unknown sources confounding environmental factors add variance. Human interference major contributor variability both within across laboratories, as well novelty-induced anxiety. Attempts reduce human measure more "natural" behaviors subjects has led...
Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors (AMPARs). In CA1 pyramidal neurons of the hippocampus two types AMPARs predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), GluA3 (GluA2/3). Whereas have been extensively studied, contribution to synapse physiology has remained unclear. Here we show in mice GluA2/3s are a low-conductance state under basal conditions, although present at synapses they contribute little currents. When intracellular...
Abstract Neuronal dysfunction due to iron accumulation in conjunction with reactive oxygen species (ROS) could represent an important, yet underappreciated, component of the epileptogenic process. However, date, alterations metabolism brain have not been addressed detail. Iron-related neuropathology and antioxidant metabolic processes were investigated resected tissue from patients temporal lobe epilepsy hippocampal sclerosis (TLE-HS), post-mortem who died after status epilepticus (SE) as...
Abstract Amyloid beta ( A β), a key component in the pathophysiology of lzheimer's disease, is thought to target excitatory synapses early disease. However, mechanism by which β weakens not well understood. Here we showed that PDZ domain protein, protein interacting with C kinase 1 PICK 1), was required for weaken synapses. In mice lacking 1, elevations failed depress synaptic transmission cultured brain slices. dissociated neurons, Aβ reduce surface...
The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer’s disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology AMPA-receptor (AMPAR) imaging mice rat neurons to demonstrate that GluA3 expression lacking is sufficient re-sensitize their damaging Aβ, indicating GluA3-containing AMPARs at necessary induce deficits. We found...