Philipp Bethge

ORCID: 0000-0003-4022-0844
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About
Contact & Profiles
Research Areas
  • Advanced Fluorescence Microscopy Techniques
  • Advanced Electron Microscopy Techniques and Applications
  • Neuroscience and Neuropharmacology Research
  • Cell Image Analysis Techniques
  • Advanced Fiber Laser Technologies
  • Semiconductor Lasers and Optical Devices
  • Photoacoustic and Ultrasonic Imaging
  • Neural dynamics and brain function
  • Retinal Development and Disorders
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Neuroscience and Neural Engineering
  • Neurogenesis and neuroplasticity mechanisms
  • Acute Ischemic Stroke Management
  • Traumatic Brain Injury and Neurovascular Disturbances
  • Muscle activation and electromyography studies
  • Sleep and Wakefulness Research
  • Alzheimer's disease research and treatments
  • Sensor Technology and Measurement Systems
  • Cellular transport and secretion
  • Medical Image Segmentation Techniques
  • Memory and Neural Mechanisms
  • Solid State Laser Technologies
  • Neurobiology and Insect Physiology Research
  • Vestibular and auditory disorders
  • Optical measurement and interference techniques

University of Zurich
2017-2024

ETH Zurich
2019-2024

Institut Interdisciplinaire de Neuroscience
2013-2016

Université de Bordeaux
2013-2016

Centre National de la Recherche Scientifique
2013-2016

Leibniz Institute for Neurobiology
2011-2013

Abstract Synaptic plasticity in the autoassociative network of recurrent connections among hippocampal CA3 pyramidal cells is thought to enable storage episodic memory. Impaired memory an early manifestation cognitive deficits Alzheimer’s disease (AD). In APP/PS1 mouse model AD amyloidosis, we show that associative long-term synaptic potentiation (LTP) abolished at stage. This caused by activation upregulated neuronal adenosine A 2A receptors (A R) rather than dysregulation NMDAR signalling...

10.1038/ncomms11915 article EN cc-by Nature Communications 2016-06-17

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model fibrinolytic treatment to show that LMCs maintain cerebral autoregulation allow for gradual reperfusion, resulting small infarcts. In mice poor LMCs, distal arterial...

10.1016/j.neuron.2024.01.031 article EN cc-by-nc-nd Neuron 2024-02-26

Abstract In 2015, we launched the mesoSPIM initiative, an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, demand imaging larger samples at higher speed and resolution has increased, requiring major improvements in capabilities such microscopes. Here, introduce next-generation (“Benchtop”) with a significantly increased field view, improved resolution, throughput, affordable cost, simpler assembly compared to original version. We...

10.1038/s41467-024-46770-2 article EN cc-by Nature Communications 2024-03-27

Many cellular structures and organelles are too small to be properly resolved by conventional light microscopy. This is particularly true for dendritic spines glial processes, which very small, dynamic, embedded in dense tissue, making it difficult image them under realistic experimental conditions. Two-photon microscopy currently the method of choice imaging thick living tissue preparations, both acute brain slices vivo. However, spatial resolution a two-photon microscope, limited ∼350 nm...

10.1016/j.bpj.2012.12.054 article EN cc-by-nc-nd Biophysical Journal 2013-02-01

Genetically encoded calcium indicators (GECIs) enable imaging of in vivo brain cell activity with high sensitivity and specificity. In contrast to viral infection or utero electroporation, indicator expression transgenic reporter lines is induced noninvasively, reliably, homogenously. Recently, Cre/tTA-dependent mice were introduced, which provide high-level green fluorescent GECIs a cell-type-specific inducible manner when crossed Cre tTA driver mice. Here, we generated characterized the...

10.1371/journal.pone.0179460 article EN cc-by PLoS ONE 2017-06-22

We use an ultrafast diode-pumped semiconductor disk laser (SDL) to demonstrate several applications in multiphoton microscopy. The SDL is based on optically pumped Vertical External Cavity Surface Emitting Laser (VECSEL) passively mode-locked with a saturable absorber mirror (SESAM) and generates 170-fs pulses at center wavelength of 1027 nm repetition rate 1.63 GHz. the suitability this for structural functional vivo imaging both Drosophila larvae mice variety fluorophores (including...

10.1364/boe.8.003213 article EN cc-by Biomedical Optics Express 2017-06-13

Abstract Neuronal networks of the mammalian motor cortex (M1) are important for dexterous control limb joints. Yet it remains unclear how encoding joint movement in M1 depends on varying environmental contexts. Using calcium imaging we measured neuronal activity layer 2/3 forelimb region while mice grasped regularly or irregularly spaced ladder rungs during locomotion. We found that population coding movements is sparse and varies according to flexibility demanded from individual joints...

10.1038/s41467-019-12670-z article EN cc-by Nature Communications 2019-10-23

In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and the capacity importin- mediated activity-dependent nuclear import. However, there is surprising paucity data showing import such proteins cellular models learning memory. Only recently it was found transcription factor cyclic AMP response element binding 2 (CREB2) transits nucleus during long-term depression (LTD), but not...

10.1371/journal.pone.0017276 article EN cc-by PLoS ONE 2011-02-18

Sleep debt accumulates during wakefulness, leading to increased slow wave activity (SWA) sleep, an encephalographic marker for sleep need. The use-dependent demands of prior wakefulness increase SWA locally. However, the circuitry and molecular identity this "local sleep" remain unclear. Using pharmacology optogenetic perturbations together with transcriptomics, we find that cortical brain-derived neurotrophic factor (BDNF) regulates via activation tyrosine kinase B (TrkB) receptor...

10.1016/j.celrep.2024.114500 article EN cc-by Cell Reports 2024-07-01

Abstract During human surgeries and autopsies, specimens are regularly sampled stored as formalin-fixed paraffin-embedded (FFPE) tissue blocks. Diagnoses rendered by microscopical examination of two-dimensional sections. Good clinical practice requires that samples be retained for decades, thus giving rise to enormous archives healthy diseased tissues. Tissue-clearing technologies whole-mount microscopy would enable 3D analyses, but whole FFPE blocks often unsuitable clearing due their size,...

10.1101/2025.05.21.655358 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2025-05-26

The inherent complexity of brain tissue, with cells intertwining locally and projecting to distant regions, has made three-dimensional visualization intact brains a highly desirable but challenging task in neuroscience. natural opaqueness tissuehas traditionally limited researchers techniques short single cell resolution such as computer tomography or magnetic resonance imaging. By contrast, single-cell required mechanical slicing into thin sections, which entails tissue distortions that...

10.3389/fnana.2019.00013 article EN cc-by Frontiers in Neuroanatomy 2019-02-13

The lower stations of the auditory system display a complex anatomy. inner ear labyrinth is composed several interconnecting membranous structures encased in cavities temporal bone, and cerebellopontine angle contains fragile such as meningeal folds, choroid plexus (CP), highly variable vascular formations. For this reason, most histological studies have either focused on or CNS by physically detaching bone from brainstem. However, neuroimmune interactions pinpointed importance meninges CP;...

10.3389/fnana.2019.00015 article EN cc-by Frontiers in Neuroanatomy 2019-02-13

In 2015, we launched the mesoSPIM initiative (www.mesospim.org), an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, demand imaging larger samples at higher speed and resolution has increased, requiring major improvements in capabilities microscopy. Here, introduce next-generation ("Benchtop") with significantly increased field view, improved resolution, throughput, affordable cost simpler assembly compared to original version. We...

10.1101/2023.06.16.545256 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-06-21

Abstract Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels yet unknown functions. Utilizing a thrombin-based mouse model and gold standard fibrinolytic treatment rt-PA, we here show that LMCs play critical role in preserving vascular function territories. We applied laser speckle contrast imaging, ultrafast ultrasound, two-photon microscopy, to after...

10.1101/2023.02.25.529915 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2023-02-27

Summary Learning goal-directed behavior requires association of pertinent sensory stimuli with behaviorally relevant outcomes. In the mammalian neocortex, dendrites pyramidal neurons are suitable sites 1–3 but how their activities adapt during learning remains elusive. Here, we track calcium signals in apical layer 5 (L5) mouse barrel cortex texture discrimination 4 . We observe diverse task-related responses, either localized to branches or widespread throughout tuft. However, even expert...

10.1101/2021.12.28.474360 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2021-12-28

The choroid plexus (CP) acts as a regulated gate between blood and cerebrospinal fluid (CSF). Despite its simple histology (a monostratified cuboidal epithelium overlying vascularized stroma), this organ has remarkably complex functions several of which involve local interaction with cells located around ventricle walls. Our knowledge CP structural organization is mainly derived from resin casts, capture the overall features but only allow reconstruction vascular pattern surface, unrelated...

10.3389/fcell.2021.692617 article EN cc-by Frontiers in Cell and Developmental Biology 2021-07-29

Background:In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and the capacity importin-mediated activitydependent nuclear import.However, there is surprising paucity data showing import such proteins cellular models learning memory.Only recently it was found transcription factor cyclic AMP response element binding 2 (CREB2) transits nucleus during long-term depression (LTD),...

10.1371/annotation/8d9dd14e-08f6-4f7e-b881-ba2839724e23 article EN cc-by PLoS ONE 2011-03-01

Abstract Progress in microscopy technology has a long history of triggering major advances neuroscience. Super-resolution (SRM), famous for shattering the diffraction barrier light microscopy, is no exception. SRM gives access to anatomical designs and dynamics nanostructures, which are impossible resolve using conventional from elaborate anatomy neurons glial cells, organelles molecules inside them. In this review, we will mainly focus on particular technique (STED microscopy), explain...

10.1515/nf-2021-0004 article EN Neuroforum 2021-03-18

Abstract Non-invasive imaging techniques, such as ultra-high field fMRI, are intricately connected to the underlying vasculature and approaching ever higher resolutions. For analysis of fMRI signals over cortical depth at high resolutions, microvascular differences might have be taken into account. Therefore, a better understanding laminar distribution interareal in is becoming more important. However, comparison cyto- myeloarchitecture, study angioarchitecture has received far less...

10.1101/2024.08.26.609648 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-08-26

Neuronal networks of the mammalian motor cortex (M1) are important for dexterous control limb joints. Yet it remains unclear how encoding joint movement in M1 depends on varying environmental contexts. Using calcium imaging we measured neuronal activity layer 2/3 mouse forelimb region while mice grasped either regularly or irregularly spaced ladder rungs during locomotion. We found that population coding movements is sparse and varies according to flexibility demanded from them regular...

10.1101/588129 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2019-03-25
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