Topic: light-sheet microscopy

FoxP genes have been linked to autism spectrum disorder (ASD), a neurodevelopmental disorder that is associated with aberrant connectivity of neural circuits. There is evidence that mutations in FoxP genes lead to impaired cognition, speech, and motor abilities. The goal of our work is to elucidate and characterize distinct molecular mechanisms with which FoxP genes orchestrate neural circuit formation. As a first step, we characterized the temporal and spatial expression pattern of the FoxP transcription factors. To study their impact on neural circuit assembly, we are using the chicken embry

Studies have linked prenatal nicotine exposure to neurobehavioral defects, including attention deficit hyperactivity disorder, behavioral issues and depression. Nicotine binds highly to the nicotinic acetylcholine receptors (nAChRs) in the habenula, perturbing cholinergic signaling. The evolutionary conserved habenula contains the largest density of nAChRs and is known as the aversive brain due to its role in mediating stress, fear and anxiety. Our research aims to understand how cholinergic signaling modulates the activity and function of the habenula. For this aim, we have generated zebra

Tissue clearing combined with light-sheet microscopy is gaining popularity among neuroscientists interested in unbiased assessment of their samples in 3D volume, while the analysis of such data remains a challenge. ClearMap and CellFinder are tools for analysing neuronal activity maps in an intact volume of cleared mouse brains. However, these tools lack a user interface, restricting accessibility primarily to scientists proficient in advanced Python programming. The present application aims to bridge this gap and make the data analysis accessible for a wider scientific community. We develop

Traditional histology relies on thin sections of small samples for studying human tissues, which limits our understanding of the complex structure and anatomical relationships of whole organs. Gross anatomy and medical imaging on the other hand lack the resolution and specificity to visualize histological structures. Tissue clearing methods are emerging as innovative solutions to transcend this constraint by revealing the spatial architecture of large tissues samples. However, making adult human organs transparent remains a challenge, given their size, density and endogenous fluorescence. We h

Cajal-Retzius (CR) cells are essential players in early brain development. In the first postnatal week (P0-P7), these glutamatergic cells densely populate the most superficial layer of the cerebral cortex, providing a transient source of excitatory inputs to immature pyramidal neurons. In the murine brain, CR cells are greatly reduced in the neocortex after postnatal week two, whereas in hippocampus, they persist throughout postnatal development and even into adulthood. During this time, they are integrated in the CA1 network, and recent work (Glærum et al. 2024) has showed that their persiste

Neuropsychiatric disorders are prevalent diseases whose causes and mechanisms remain unknown due to its complexity. In this context, translating experimental findings from humans to the clinic represents a major challenge that new technologies are assessing. Here we propose the use of a neurohistopathology pipeline to perform systematic multiscale analysis of pathological human brains and identify the cellular, molecular and circuit underpinnings of neurodegenerative and psychiatric disorders. We have developed and adapted new tissue clearing and labeling techniques in large scale samples, whi

Tissue-clearing in combination with light-sheet microscopy enabled scientists to observe entire organs and animals without the necessity of histological sectioning. However, the variety of different tissue-clearing methods often ponders the question of which protocol to use. Here we provide the chemical fundamentals for dehydration-based tissue-clearing approaches and show important, yet neglected parameters, for preserving morphology and drastically improving tissue transparency and light transmission. These parameters are the polarity of the dehydration agent, color of the tissue-cleared sam

Navigating through a vivid environment requires animals to rapidly process a bewildering mass of sensory signals and interpret it in the context of ongoing behavior. Local and global motion cues along with luminance information guide them to orient and interact adaptively within the world. Larval zebrafish react to such signals with behaviors ranging from active light seeking and shadow avoidance to optomotor swimming or hunting that are expressed in kinematically distinct movements. We asked how are the brain-wide networks of neurons organized that process such signals and how do they integra

Understanding brain function in health and disease requires unbiased three-dimensional mapping of its neurochemical architecture. Traditional histological methods require mechanical tissue sectioning, leading to cutting artefacts, lengthy processing times and loss of crucial three-dimensional information. To overcome that, optical clearing techniques have soared since 3DISCO allowed us to visualise neuronal networks in the whole mouse brain1. Immunolabelling in whole organs is possible; however, antibody penetration is a challenge and most clearing protocols are tailored for mice or human tiss

The brain encodes and adapts to living environments. Brain function is maintained by interactions between neurons and glia, among which astrocytes relay important information in physiological and pathological responses. Understanding astrocyte signaling in specific life contexts will help to complete an integrative view about brain action. Energy homeostasis is the basis for the sustainability of life being. The brain hypothalamic nuclei play prominent roles in orchestrating body energy states, yet the signaling features of astrocytes remain to be characterized. Astrocytes display calcium dyna

Fear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, detailed knowledge of the neural circuitry modulating fear memory could be the turning point for the comprehension of this emotion and its pathological states. A comprehensive understanding of the circuits mediating memory encoding, consolidation, and retrieval presents the fundamental technological challenge of analyzing activity in the entire brain with single-neuron resolution. In this context, we develop the brain-wide neuron quantification toolkit (BRANT) for mapping whole-brain neuronal activati