A5051915877- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Advanced Memory and Neural Computing
- Photoreceptor and optogenetics research
- Electrochemical Analysis and Applications
- Connexins and lens biology
- Autism Spectrum Disorder Research
- Neonatal and fetal brain pathology
- Hearing, Cochlea, Tinnitus, Genetics
- Genetics and Neurodevelopmental Disorders
- Sleep and Wakefulness Research
- Receptor Mechanisms and Signaling
- EEG and Brain-Computer Interfaces
- Nicotinic Acetylcholine Receptors Study
- Advanced Fluorescence Microscopy Techniques
- Vestibular and auditory disorders
- Cannabis and Cannabinoid Research
Institute of Molecular and Clinical Ophthalmology Basel
2021-2025
Vrije Universiteit Amsterdam
2015-2022
Australian National University
2021-2022
Harvard University
2020-2021
Howard Hughes Medical Institute
2020-2021
Amsterdam Neuroscience
2011-2018
Netherlands Institute for Neuroscience
2014
Erasmus MC
2014
Royal Netherlands Academy of Arts and Sciences
2014
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013
The size and shape of dendrites axons are strong determinants neuronal information processing. Our knowledge on structure function is primarily based brains laboratory animals. Whether it translates to human not known since quantitative data "full" morphologies lacking. Here, we obtained brain tissue during resection surgery reconstructed basal apical individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, did correlate etiology, disease severity, or...
The advanced cognitive capabilities of the human brain are often attributed to our recently evolved neocortex. However, it is not known whether basic building blocks neocortex, pyramidal neurons, possess unique biophysical properties that might impact on cortical computations. Here we show layer 2/3 neurons from temporal cortex (HL2/3 PCs) have a specific membrane capacitance ( C m ) ~0.5 µF/cm 2 , half commonly accepted 'universal' value (~1 for biological membranes. This finding was...
Significance The cerebellum has long been recognized as a partner of the cerebral cortex, and both have expanded greatly in human evolution. thin cerebellar cortex is even more tightly folded than cortex. By scanning specimen at ultra-high magnetic fields, we were able to computationally reconstruct its surface down level smallest folds, revealing that almost 80% area performing same procedure on monkey brain, found suggesting role characteristically behaviors, such toolmaking language.
Because of fast recovery from synaptic depression and fast-initiated action potentials, neuronal information transfer can have a substantially higher bandwidth in human neocortical circuits than those rodents.
The neocortex in our brain stores long-term memories by changing the strength of connections between neurons. To date, rules and mechanisms that govern activity-induced synaptic changes at human cortical synapses are poorly understood have not been studied directly a cellular level. Here, we made whole-cell recordings pyramidal neurons slices tissue resected during neurosurgery to investigate spike timing-dependent plasticity adult neocortex. We find can undergo bidirectional modifications...
We present detailed models of pyramidal cells from human neocortex, including on their excitatory synapses, dendritic spines, NMDA- and somatic/axonal Na+ spikes that provided new insights into signal processing computational capabilities these principal cells. Six layer 2 3 (HL2/L3 PCs) were modeled, integrating anatomical physiological data both fresh postmortem tissues temporal cortex. The predicted particularly large AMPA- NMDA-conductances per synaptic contact (0.88 1.31 nS,...
Neuronal theories of neurodevelopmental disorders (NDDs) autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks the Fmr1-KO mouse model for autism. In line with predictions from neurocognitive theory, we found neighboring were hyperconnected during a critical period early mPFC development....
Abstract A variety of inhibitory pathways encompassing different interneuron types shape activity neocortical pyramidal neurons. While basket cells (BCs) mediate fast lateral inhibition between neurons, Somatostatin-positive Martinotti (MCs) a delayed form inhibition. Neocortical circuits are under control acetylcholine, which is crucial for cortical function and cognition. Acetylcholine modulates MC firing, however, precisely how cholinergic inputs affect not known. Here, we find that...
Abstract Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic pyramidal neurons layers 2 and 3 using neurosurgically resected middle temporal gyrus (MTG, Brodmann area 21), which part distributed language circuitry. find that local connectivity comparable with mouse layer 2/3 connections anatomical homologue (temporal association area), are 3-fold stronger more reliable (0%...
Photoactivated genetically encoded voltage indicators (GEVIs) have the potential to enable optically sectioned imaging at intersection of a photoactivation beam and an beam. We developed pooled high-throughput screen identify archaerhodopsin mutants with enhanced photoactivation. After screening ~10 5 cells, we identified novel GEVI, NovArch, whose one-photon near-infrared fluorescence is reversibly by weak blue or two-photon excitation. Because leads fluorescent signals catalytically rather...
Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter magnitude sign depend millisecond timing of presynaptic postsynaptic action potential firing. Recent findings laboratory animals have shown that neurons show a variety temporal windows for spike-timing-dependent plasticity (STDP). It is unknown what synaptic learning rules exist human synapses whether...
Summary Engineering infrared light sensitivity in the blind human retina could restore visual function patients with regional retinal degeneration. However, current approaches are complex and contain non-human biological components. Using rational protein design we engineered TRPV1 channels (Δ786-840) temperature shifted from 45 to 41°C that enabled near-infrared light- induced heat activation of mammalian cells at close physiological temperatures. When expressed ganglion explants, Δ786-840...
Endocannabinoids control hippocampal inhibitory synaptic transmission through activation of presynaptic CB 1 receptors. During depolarization-induced suppression inhibition (DSI), endocannabinoids are synthesized upon postsynaptic depolarization. The endocannabinoid 2-arachidonoylglycerol (2-AG) may mediate DSI. Currently, the best studied pathway for biosynthesis 2-AG involves enzyme diacylglycerol lipase (DAGL). However, whether DAGL is necessary DSI controversial and was not...
Abstract We present the first-ever detailed models of pyramidal cells from human neocortex, including on their excitatory synapses, dendritic spines, NMDA- and somatic/axonal- Na + spikes that provided new insights into signal processing computational capabilities these principal cells. Six layer 2 3 (HL2/L3 PCs) were modeled, integrating anatomical physiological data both fresh post mortem tissues temporal cortex. The predicted particularly large AMPA- conductances per synaptic contact...
ABSTRACT The recent positively tuned ASAP4-family voltage indicators feature superior photostability compared to the negatively ASAP3, but signal-to-noise ratios (SNRs) for spike detection were not significantly different. To improve by ASAP indicators, we performed multiple rounds of structure-guided saturation mutagenesis an ASAP4 template while screening directly faster responses. Our resulting variants, ASAP6.1 and ASAP6b, demonstrated sufficient dynamic range kinetics, reported action...
Dense sampling of voxels limits time resolution in two-photon microscopy. We developed a system to scan sequentially through 512 excitation spots at 2 microseconds between spots, enabling targeted recording neurotransmitter release millisecond intact tissue.
Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, have only just started to describe human brain. Here investigate capacity neurons generate NMDA spikes. We find that dendritic iontophoresis glutamate, as well local stimulation, can evoke spikes layer 2/3 pyramidal neurons. However, was significantly reduced compared rodent Simulations morphologically realistic and simplified models indicated a higher...
Summary Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, have only just started to describe human brain. Here investigate capacity neurons generate NMDA spikes. We find that dendritic iontophoresis glutamate, as well local stimulation, can evoke spikes layer 2/3 pyramidal neurons. Surprisingly, however, was significantly reduced compared rodent Simulations morphologically realistic models indicated a...