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Graham Knott

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Related publications (101)

Modeling Brain Circuitry over a Wide Range of Scales

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is nee ...

Frontiers Research Foundation2015

Delayed and Temporally Imprecise Neurotransmission in Reorganizing Cortical Microcircuits

Graham Knott, Anne Alison Jorstad, Yan Liu, Yuan Liu

Synaptic neurotransmission is modified at cortical connections throughout life. Varying the amplitude of the postsynaptic response is one mechanism that generates flexible signaling in neural circuits. The timing of the synaptic response may also play a ro ...

Soc Neuroscience2015

PGC-1 alpha activity in nigral dopamine neurons determines vulnerability to alpha-synuclein

Bernard Schneider, Graham Knott, Wojciech Janusz Bobela, Lu Zheng

Introduction: Mitochondrial dysfunction and oxidative stress are critical factors in the pathogenesis of age-dependent neurodegenerative diseases. PGC-1 alpha, a master regulator of mitochondrial biogenesis and cellular antioxidant defense, has emerged as ...

2015

NeuroMorph: A Toolset for the Morphometric Analysis and Visualization of 3D Models Derived from Electron Microscopy Image Stacks

Pascal Fua, Graham Knott, Corrado Cali, Biagio Nigro, Anne Alison Jorstad, Marta Wawrzyniak

Serial electron microscopy imaging is crucial for exploring the structure of cells and tissues. The development of block face scanning electron microscopy methods and their ability to capture large image stacks, some with near isotropic voxels, is proving ...

Humana Press2015

Pansynaptic Enlargement at Adult Cortical Connections Strengthened by Experience

Graham Knott

Behavioral experience alters the strength of neuronal connections in adult neocortex. These changes in synaptic strength are thought to be central to experience-dependent plasticity, learning, and memory. However, it is not known how changes in synaptic tr ...

Oxford University Press2014

Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration

Liliane Glauser, Graham Knott, Darren Moore, Elpida Tsika, Meghna Kannan, Shi-Yan Caroline Foo

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). The clinical and neurochemical features of LRRK2-linked PD are similar to idiopathic disease although neuropathology is somewhat heter ...

Elsevier2014

The Relationship between PSD-95 Clustering and Spine Stability In Vivo

Graham Knott, Bohumil Maco

The appearance and disappearance of dendritic spines, accompanied by synapse formation and elimination may underlie the experience-dependent reorganization of cortical circuits. The exact temporal relationship between spine and synapse formation in vivo re ...

Soc Neuroscience2014

Semiautomated correlative 3D electron microscopy of in vivo-imaged axons and dendrites

Marco Cantoni, Graham Knott, Bohumil Maco

This protocol describes how in vivo-imaged dendrites and axons in adult mouse brains can subsequently be prepared and imaged with focused ion beam scanning electron microscopy (FIBSESEM). The procedure starts after in vivo imaging with chemical fixation, f ...

Nature Publishing Group2014

FOXO3 determines the accumulation of alpha-synuclein and controls the fate of dopaminergic neurons in the substantia nigra

Juan-Carlos Sarria, Bernard Schneider, Graham Knott, Emilda Pino, Lu Zheng, Ryoji Amamoto

Parkinson's disease (PD) is characterized by the selective degeneration of neuronal populations presumably due to pathogenic interactions between aging and predisposing factors such as increased levels of a-synuclein. Here, we genetically modulate the acti ...

Oxford University Press2014

Connexin 30 sets synaptic strength by controlling astroglial synapse invasion

Nicole Déglon, Graham Knott

Astrocytes play active roles in brain physiology by dynamic interactions with neurons. Connexin 30, one of the two main astroglial gap-junction subunits, is thought to be involved in behavioral and basic cognitive processes. However, the underlying cellula ...

Nature Publishing Group2014

Correlative In Vivo 2-Photon Beam Scanning Electron Microscopy: 3D Analysis of Neuronal Ultrastructure

Pascal Fua, Graham Knott, Bohumil Maco, Anne Alison Jorstad

This protocol describes how dendrites and axons, imaged in vivo, can subsequently be analyzed in 3D using focused ion beam scanning electron microscopy (FIBSEM). The fluorescent structures are identified after chemical fixation and their position highlight ...

Elsevier Academic Press Inc2014

Efficient scanning for em based target localization

Pascal Fua, Graham Knott, Raphael Sznitman, Aurélien Lucchi

We presented an approach for speeding-up image acquisition when tasked with localizing specific structures in FIB-SEM imagery. It exploits the fact that low-quality images can be acquired faster than higher-quality ones and yet be sufficient for inference ...

2014

SAS-1 Is a C2 Domain Protein Critical for Centriole Integrity in C. elegans

Simon Blanchoud, Graham Knott, Pierre Gönczy, Tamara Mikeladze-Dvali, Lukas von Tobel

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sp ...

Public Library of Science2014

Mitonuclear protein imbalance as a conserved longevity mechanism

Graham Knott, Elena Katsyuba, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Dongryeol Ryu, Laurent Mouchiroud

Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial riboso ...

Nature Publishing Group2013

Imaging green fluorescent protein-labeled neurons using light and electron microscopy

Graham Knott

The ability to observe axons and dendrites with transmission electron microscopy (EM) after they have been previously imaged live with laser-scanning microscopy is a useful technique to study their synaptic connectivity. This protocol provides a detailed m ...

2013

Universal sample holder

Graham Knott

This device is for holding samples during their preparation prior to imaging in the electron microscope. The design means it can be transferred between the light and electron microscopes as well as trimming devices used to prepare the final sample. It can ...

2013

In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits

Graham Knott, Bohumil Maco

To what extent, how and when axons respond to injury in the highly interconnected grey matter is poorly understood. Here we use two-photon imaging and focused ion beam-scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity o ...

Nature Research2013

Altered Synaptic Dynamics during Normal Brain Aging

Graham Knott, Bohumil Maco

What is the neuroanatomical basis for the decline in brain function that occurs during normal aging? Previous postmortem studies have blamed it on a reduction in spine density, though results remain controversial and spine dynamics were not assessed. We us ...

Soc Neuroscience2013

Flash Scanning Electron Microscopy

Pascal Fua, Marco Cantoni, Graham Knott, Raphael Sznitman, Aurélien Lucchi

Scanning Electron Microscopy (SEM) is an invaluable tool for biologists and neuroscientists to study brain structure at the intra- cellular level. While able to image tissue samples with up to 5nm isotropic resolution, image acquisition is prohibitively sl ...

2013

BMP signaling specifies the development of a large and fast CNS synapse

Graham Knott, Ralf Schneggenburger, Le Xiao, Elin Kristina Kronander, Enida Gjoni

excitatory synapses with multiple active zones ensure reliable and fast information transfer at specific points in neuronal circuits. However, the mechanisms that determine synapse size in CNS circuits are largely unknown. Here we use the calyx of Held syn ...

Nature Publishing Group2013

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