Electron microscopy

…multi-axis sample manipulation across electron microscopy, spectroscopy, diffraction, probing, nanoindentation and tomography. SmarAct’s customizable SEM platform illustrates approaches to alignment, measurement geometry and transitions between techniques, including in-situ experiments. The emphasis is on how adaptable manipulation enables complementary measurements to build a fuller accoun

A workshop for research technical professionals examines electron microscopy, sample preparation and the operation of research facilities. Presentations cover imaging, spectroscopy, cryo-SEM, data quality, industrial microscopy and post-irradiation examination; discussion addresses maintenance, standard operating procedures, data management and user training. Participants compare technical practices and develop collaborations across the UK microscopy community. The 17 November programme begins with arrival at 09:30, followed by a 10:00 welcome, two presentation sessions, a panel at 15:15 and c

…and protein expression onto reference electron microscopy connectomes and uses them to study the development and organisation of sexually dimorphic circuits. The postdoc researches the development and function of neural circuits, develops and applies techniques, presents work at seminars and meetings, drafts papers and helps train PhD stude

Over the past decade our community has made substantial progress in the construction of anatomically detailed network models of the cortical tissue. Thanks to advances in computer hardware and simulation technology, researchers can now routinely work with these models at the natural density of neurons and synapses. Moreover, the availability of cloud services means that such investigations can be carried out without having to install either the model or the simulation software. A recent workshop analyzed the impact of a specific model of the cortical microcircuit, published ten years ago . The

Sensory feature maps are a key building block in the information-processing infrastructure of the nervous system. However, our understanding of how such maps interface with motor circuits to produce behavior at rapid timescales remains poor. Here, we examine this problem through the lens of flight control in Drosophila melanogaster. Underlying the extraordinary aerial agility of the fruit fly is mechanosensory feedback from the haltere, a reduced hindwing that acts as both a biological gyroscope and an adjustable clock to set the spike-timing of wing-steering motor neurons. Although the halter

Connectomes provide critical constraints for neural circuit models. Advances in electron microscopy have dramatically increased the scale of connectome datasets, enabling more realistic modeling of neural circuits. However, challenges remain in using these datasets. Many models still rely on unconstrained physiological parameters, even within fully mapped circuits, leading to ongoing debates about the predictive power of connectomic data. Key questions remain on how synaptic connectivity relates to physiological properties and the anatomical detail needed to predict function. One modeling choi

Body size varies across 21 orders of magnitudes in the animal kingdom [1]. In contrast to most organs, which scale through the proliferation of dividing cells of similar size, brains expand by modulating the size of non-dividing neuronal cells to innervate space during development [2]. Consequently, there is a notable variation in neuronal size and structure within individual brains and across species [3]. Considering that size inherently affects the rates of biological structures and processes, from cellular metabolism to information processing [4], the ability of neurons to maintain essentia

Microcircuits are the fundamental building blocks of the neocortex [1]. Single instances have been reconstructed experimentally (e.g., [2]), and their general dynamics and information processing capabilities have been investigated theoretically (e.g., [3, 4, 5, 6, 7]). Their architecture is usually represented in connectivity maps consisting of probabilities that neurons establish connections. These maps reduce the complicated circuitry to simple relations between cell types, allowing for efficient instantiations of neural network models in parallel computers [8]. While this approach neglects

…Using electron microscopy-based reconstructions, we investigate how circuits transform mechanical stimulations into location-appropriate behavior. We previously described the somatotopic organization of bristle mechanosensory neurons (BMNs) around the Drosophila head that elicit a

When larval zebrafish experience whole-field visual motion, as in the random-dot task, they swim in the direction of motion - an innate behavior enabling animals to maintain position in moving water. This behavior is well-explained by the same drift-diffusion algorithm that captures human and primate behavior in analogous random-dot paradigms. We previously proposed a hypothetical circuit model that implements this algorithm via a recurrent integrator circuit in the zebrafish hindbrain that accumulates noisy visual evidence and excites downstream motor circuits after overcoming competitive inh

…including in utero electroporation, electron microscopy and electrophysiology, we reveal a tight correlation in the distribution

The human brain is an extremely complex network of ~80 billion neurons, and it underpins all thoughts and emotions through coordinated neural activity. The underlying network changes with age and environment, and it is vulnerable to perturbations. Our goal is to understand both normal and pathological neural networks at the level of individual neurons, and how human illnesses affect them.Studying human neurodevelopmental disorders is often challenging using animal models. By using cerebral organoids from induced pluripotent stem cells (iPS), we can investigate these conditions in sophisticated

The activity-regulated gene Arc/Arg3.1 is known for its vital role in memory consolidation and synaptic plasticity [1]. Our recent research revealed a novel role for Arc/Arg3.1 in developing brain circuits. In the hippocampus, a spontaneous wave of Arc/Arg3.1 upregulation is observed during the first postnatal month, crucial for establishing proper spatial learning and intact hippocampal oscillations in adult mice [2]. Since the emergence of hippocampal oscillatory rhythms relies on an intricate interplay between excitatory and inhibitory synaptic connections, we hypothesized that early postna

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. Subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning and memory in many brain areas including the hippocampus, and are implicated in neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) and hippocampo-septal cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal tar

Tissue plasminogen activator (tPA) is a protease expressed in CNS by various cells and it is mainly known for its thrombolytic function in the treatment of stroke. While its contribution to myelination within the central nervous system is known, its involvement in peripheral remyelination processes remains to be explored. Indeed, in physiological conditions, Schwann cells, responsible for myelination, express low levels of tPA, however its expression increases following injuries to peripheral nerves. Therefore, our study focused on elucidating involvement of tPA in peripheral nervous system re

Mapping the spatial patterns of synaptic connectivity is essential for understanding neural circuit function. Two-photon optogenetics combined with whole-cell patch clamp enable synaptic circuit mapping in mammalian cortex. We consider an experimental set-up in which the experimenter patches a single target cell and uses two-photon optogenetics to stimulate surrounding tissue in a 3-dimensional grid while measuring postsynaptic currents (PSCs). This yields a high resolution spatial map of putative synaptic connections to a single neuron. However, these connectivity maps are noisy due to biolog

…hard X-ray imaging techniques, volume electron microscopy and their combination with other imaging modalities, with a forward look to areas of opportunity becoming accessible as a result of the recent and upcoming synchrotron upgrades. We expect an exciting day filled with science focused talks and lively discussions on

…and methods for correlative light/electron microscopy. They make all tools freely available to everyone and work to get them in the hands of people that have limited resources.

The "mind of the worm", the first electron microscopy-based connectome of C. elegans, was an early sign of where connectomics is headed, followed by a long time of little progress in a field held back by the immense manual effort required for data acquisition and analysis. This changed over the last few years with several technological breakthroughs, which allowed increases in data set sizes by several orders of magnitude. Brain tissue can now be imaged in 3D up to a millimeter in size at nanometer resolution, revealing tissue features from synapses to the mitochondria of all contained cells.

The Manookin lab is investigating the structure and function of neural circuits within the retina and developing techniques for treating blindness. Many blinding diseases, such as retinitis pigmentosa, cause death of the rods and cones, but spare other cell types within the retina. Thus, many techniques for restoring visual function following blindness are based on the premise that other cells within the retina remain viable and capable of performing their various roles in visual processing. There are more than 80 different neuronal types in the human retina and these form the components of

The ability of the brain to encode and store information depends on the plastic nature of the individual synapses. The increase and decrease in synaptic strength, mediated through the structural plasticity of the spine, are important for learning, memory, and cognitive function. Dendritic spines are small structures that contain the synapse. They come in a variety of shapes (stubby, thin, or mushroom-shaped) and a wide range of sizes that protrude from the dendrite. These spines are the regions where the postsynaptic biochemical machinery responds to the neurotransmitters. Spines are dynamic s