A5012972487- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Retinal Development and Disorders
- T-cell and B-cell Immunology
- Visual perception and processing mechanisms
- Immune Cell Function and Interaction
- Olfactory and Sensory Function Studies
- Photoreceptor and optogenetics research
- Neurobiology and Insect Physiology Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Axon Guidance and Neuronal Signaling
- Cell Image Analysis Techniques
- Monoclonal and Polyclonal Antibodies Research
- Advanced Fluorescence Microscopy Techniques
- Sleep and Wakefulness Research
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
- Treatment of Major Depression
- Meningioma and schwannoma management
- Cancer-related gene regulation
- Neuroscience and Neural Engineering
- Developmental Biology and Gene Regulation
- Aesthetic Perception and Analysis
- Wnt/β-catenin signaling in development and cancer
Netherlands Institute for Neuroscience
2016-2025
Amsterdam Neuroscience
2017-2024
Royal Netherlands Academy of Arts and Sciences
2015-2024
Vrije Universiteit Amsterdam
2015-2024
University of Nottingham
2021
Royal Academy of Art
2004-2019
Virginia Commonwealth University Medical Center
2012
Allen Institute for Brain Science
2008
Combined Ophthalmic Research Rotterdam
2004-2005
Center for Cancer Research
1995-1999
Loss of Crumbs homologue 1 (CRB1) function causes either the eye disease Leber congenital amaurosis or progressive retinitis pigmentosa, depending on amount residual CRB1 activity and genetic background. Crb1 localizes specifically to sub-apical region adjacent adherens junction complex at outer limiting membrane in retina. We show that it is associated here with multiple PDZ protein (Mupp1), Lin-7 (Pals1 Mpp5) Mpp4. have produced Crb1(-/-) mice completely lacking any functional Crb1....
Thymic repertoire selection requires the expression of alpha beta CD3 T-cell receptor (TCR) together with coreceptors CD4 and CD8. The appearance CD8 on thymocytes is hallmark a complex maturation step, accompanied by downregulation interleukin 2 (IL-2R) chain, arrest rearrangement (i.e., allelic exclusion) TCR beta-chain locus, burst cell divisions, reduction in size. This step inhibited beta-chain-deficient mouse strains may depend surface an immature containing chains but no chain. Here...
Pseudoxanthoma elasticum (PXE) is a heritable disorder of connective tissue, affecting mainly skin, eye and the cardiovascular system. PXE characterized by dystrophic mineralization elastic fibres. The condition caused loss function mutations in ABCC6. We generated Abcc6 deficient mice (Abcc6−/−) conventional gene targeting. As shown light electron microscopy Abcc6−/− spontaneously developed calcification fibres blood vessel walls Bruch's membrane eye. No clear abnormalities were seen dermal...
The firing rates of neurons in primary visual cortex (V1) are suppressed by large stimuli, an effect known as surround suppression. In cats and monkeys, the strength suppression is sensitive to orientation; responses regions containing uniform orientations more than those orientation contrast. This thought be important for scene segmentation, but underlying neural mechanisms poorly understood. We asked whether it possible study these mice, because recent advances technology studying cortical...
The segregation of figures from the background is an important step in visual perception. In primary cortex, evoke stronger activity than backgrounds during a delayed phase neuronal responses, but it unknown how this figure-ground modulation (FGM) arises and whether necessary for Here, we show, using optogenetic silencing mice, that V1 response segregation. Neurons higher areas also exhibit FGM reduced V1. V1, elicited vasoactive intestinal peptide-expressing (VIP) interneurons background,...
Background Inhibitory innervation by parvalbumin (PV) expressing interneurons has been implicated in the onset of sensitive period visual plasticity. Immunohistochemical analysis development and plasticity these inhibitory inputs is difficult because PV expression low young animals strongly influenced neuronal activity. Moreover, synaptic boutons that neurons form onto each other cannot be distinguished from innervated cell bodies immunostaining for this protein it present throughout cells....
In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there no clear genotype–phenotype correlation for CRB1 mutations, which suggests that other components CRB complex may influence severity retinal disease. Therefore, to understand physiological role proteins, we generated analysed conditional knockout mice lacking CRB2 developing retina. Progressive disorganization was detected...
Neurophysiological studies depend on a reliable quantification of whether and when neuron responds to stimulation. Simple methods determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based fitting hyperparameter tuning. These choices can change the results, which invites bad statistical practice reduces replicability. New recording techniques that yield increasingly large numbers cells would benefit from test for cell-inclusion...
Several recent observations suggest that successful rearrangement of the T cell receptor (TCR) beta locus induces several important events in thymocyte maturation. Allelic exclusion is achieved by interruption further locus, and CD4-8- interleukin (IL)-2R+ cells enter CD4+8+IL-2R- stage. The actual molecular regulating this control point are unknown, but may be related to expression TCR-beta immature thymocytes. It not clear whether maturation induced intracellular appearance chain or signal...
Inactivating genes in vivo is an important technique for establishing their function the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and compensatory regulation of other genes. One approach to producing conditional activation inactivation involves use Cre recombinase remove loxP-flanked segments DNA. We have studied effects delivering hippocampus neocortex by injecting replication-deficient...
ABSTRACT Down syndrome (DS) patients suffer from mental retardation, but also display enhanced β‐APP production and develop cortical amyloid plaques at an early age. As Notch are both processed by γ‐secretase, we analyzed expression of the signaling pathway in adult DS brain a model system for DS, human trisomy 21 fibroblasts quantitative PCR. In cortex found that Notch1, Dll1 Hes1 is up‐regulated. Moreover, Alzheimer disease show overexpression Notch1 Dll1, indicating processing AD could be...
Abstract The introduction of forward genetic screens in the mouse asks for techniques that make rapid screening visual function possible. Transcranial imaging intrinsic signal is suitable this purpose and could detect effects retinal degeneration, increased predominance contralateral eye albino animals. We quantified response properties cortex by introducing a normalization method to reduce impact biological noise. In addition, presentation ‘reset’‐stimulus shortly after probing stimulus at...
For many inborn errors of metabolism (IEM) the understanding disease mechanisms remains limited in part explaining their unmet medical needs. We hypothesize that expressivity IEM phenotypes is affected by activity specific modifier pathways, which controlled rare and common polygenic variation. To identify these modulating we used RNA sequencing to generate molecular signatures relevant tissues. then integrated with multiomic data gene regulatory networks generated from animal human...
In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise cortical We therefore asked whether postsynaptic BDNF signaling through receptor TrkB regulates spine persistence in V1. This question has been difficult to address because most methods used alter vivo affect development or cannot distinguish between pre- mechanisms. circumvented these problems by...
During brain development, the neocortex shows periods of enhanced plasticity, which enables acquisition knowledge and skills that we use build on in adult life. Key to persistent modifications neuronal connectivity plasticity are molecular changes occurring at synapse. Here used isobaric tag for relative absolute quantification measure levels 467 synaptic proteins a well-established model mouse visual cortex regulation its critical period. We found inducing by monocular deprivation during...