Viewing archives for Miesenböck Group
Sha Liu
Abstract: The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations remains unknown. To fill this gap, we profiled the single-cell transcriptome of adult Drosophila brains across the sleep-wake cycle and four circadian times. We show cell type-specific transcriptomic changes, with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep-wake cycle and sleep drive level affect expression of clock gene regulators in glia, while diminishing the circadian clock specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings offer a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep-wake dynamics.
Biography: Sha Liu is a group leader and assistant professor at VIB-KU Leuven Center for Brain and Disease Research. His work focuses on sleep’s cellular and synaptic functions, using fruit flies as a model system. Before starting his lab in Belgium in 2018, he was a postdoctoral fellow in Dr. Mark Wu’s lab at Johns Hopkins University, where he studied the circadian and homeostatic regulation of sleep in Drosophila.
Paul Volkmann
Gero Miesenböck awarded 2023 Japan Prize
Professor Gero Miesenböck, DPAG’s Waynflete Professor of Physiology and Director of the Centre for Neural Circuits and Behaviour, is one of two scientists to be awarded the 2023 Japan Prize “for their development of methods that use genetically addressable light-sensitive membrane proteins to unravel neural circuit function”.
Head of Department Professor David Paterson said: “The Japan Prize is a major international prize that correctly recognises the outstanding discovery that Gero Miesenböck and Karl Deisseroth made in establishing a new methodology – optogenetics – using light sensitive protein to unravel neural circuits during complex physiological tasks. This has been one of the biggest advances made in neuroscience this century.”
The Japan Prize in the field of Life Sciences rewards significant contributions to society through discoveries of new biological phenomena and elucidation of biological regulatory mechanisms as well as major advances in scientific technology that make possible deeper understanding of biological functions.
Professor Miesenböck was the first to demonstrate optogenetic control of neural activity and animal behaviour. Early in 2002, the Miesenböck group used genetic engineering to smuggle a set of opsin genes from fruit fly eyes into rat nerve cells in a dish. The researchers showed for the first time that shining a light on opsin-altered neurons could trigger the cells to fire electrical impulses. A few years later, the lab implanted light sensitive ion channels deep into the brains of fruit flies and demonstrated that optogenetics could also work in living creatures. In this experiment, light precisely stimulated two of the fly’s neurons without triggering any neighbouring neurons, and controlled the insect’s ability to fly away. Professor Miesenböck’s subsequent discoveries on the neural basis of reward, the regulation and function of sleep, and the control of sexually dimorphic behaviour proved the utility of optogenetics for neurobiological research.
Representatives of The Japan Prize Foundation Selection Committee said: “Prof Gero Miesenböck successfully devised the concept and principles underlying this technology, and demonstrated its effectiveness. Prof Karl Diesseroth then developed the technology to make it simpler and more accurate, which allowed it to be harnessed across a broad range of research fields.
“The use of light stimulation has become an indispensable tool in neuroscience research, and has led to remarkable progress in the field. It is also expected that this technique will be useful in medical applications, such as restoring sight for the blind and developing treatments for Parkinson’s disease.”
More information about the 2023 Prize and its winners can be found on the Japan Prize website.
Cecilia Velasco Dominguez
William Wisden
Abstract: Wisden will present evidence that certain types of stress can induce a restorative sleep. This is mediated by sleep-inducing circuitry in the midbrain and, in particular, inhibitory GABAergic neurons in the ventral tegmental area. A specific circuit allows animals to restore mental and body functions by sleeping, potentially providing a refined route for treating anxiety disorders. Wisden will also present unpublished findings on basal ganglia circuitry that generates REM sleep and how this REM circuitry can modulate anxiety.
Biography: William Wisden studied Natural Sciences at the University of Cambridge and then completed a PhD with Stephen Hunt at the MRC Molecular Neurobiology Unit, Cambridge, followed by a postdoc in Peter Seeburg’s lab at the University of Heidelberg, Germany. He returned to Cambridge as a group leader at the MRC Laboratory of Molecular Biology, followed by another period at the University of Heidelberg, then a Professorship at the University of Aberdeen, and in 2009 he moved to Imperial College London where he has been ever since. Wisden has worked extensively on GABA and glutamate receptors, initially their cloning and molecular characterization, and then later using mouse genetics to understand how these receptors work in various circuitries. Since around 2009, in collaboration with Nick Franks (also at Imperial), he has investigated sleep-wake circuitry and the homeostatic drive to sleep.
Stephane Dissell
Abstract: Sleep is a complex and plastic behavior regulated by multiple brain regions and influenced by numerous internal and external factors. Thus, to fully uncover the function(s) of sleep, cellular resolution of sleep-regulating neurons needs to be achieved. In the Drosophila brain, neurons projecting to the dorsal Fan-Shaped Body (dFB) have emerged as a key sleep-regulating area. To dissect the contribution of individual dFB neurons to sleep, we undertook an intersectional Split-GAL4 genetic screen focusing on cells contained within the 23E10-GAL4 driver, the most widely used tool to manipulate dFB neurons. We demonstrate that 23E10-GAL4 expresses in neurons outside the dFB and in the fly equivalent of the spinal cord, the Ventral Nerve Cord (VNC), and show that two VNC cholinergic neurons strongly contribute to the sleep-promoting capacity of the 23E10-GAL4 driver under baseline conditions. However, in contrast to other 23E10-GAL4 neurons, silencing these VNC cells does not block sleep homeostasis. Thus, our data demonstrate that the 23E10-GAL4 driver contains at least two different types of sleep-regulating neurons controlling distinct aspects of sleep. Our work highlights the importance of using tools (GAL4 drivers in this case) that are as specific as possible when trying to link a behavior with a neuron or group of neurons.
Biography: Stephane Dissel was an undergraduate researcher in Jules Hoffmann’s laboratory in Strasbourg before completing his PhD under Charalambos Kyriacou at the University of Leicester, where he studied the role of the circadian photoreceptor CRYPTOCHROME in clock neurons. As a postdoctoral fellow in the laboratory of Paul Shaw at Washington University in St. Louis he demonstrated that increasing sleep by genetic or pharmacological means could reverse memory deficits in classical memory mutants or in fly models of Alzheimer’s disease. He launched his independent group at the University of Missouri–Kansas City in 2018.
Andrew Lin
Abstract:
How do brains form stimulus-specific memories? We previously showed that in the fruit fly Drosophila, the odour-specificity of olfactory associative memories is enabled by sparse coding in the Kenyon cells of the mushroom body, i.e., only a small fraction of Kenyon cells responds to each odour. Too much Kenyon cell activity leads to failures to discriminate between similar odours, but too little activity could lead to detection failures – how do Kenyon cells achieve the correct ‘Goldilocks’ level of activity? The answer may lie in part in homeostatic plasticity: we found that the mushroom body circuitry homeostatically compensates for prolonged (4 d) excess inhibition, using a combination of reducing inhibition and increasing excitation. In addition, our computational models show that given the natural variability between Kenyon cells in network parameters governing excitability, the network performs best if variability in one parameter compensates for variability in another (e.g., Kenyon cells with few excitatory inputs have stronger excitatory inputs). Indeed, correlations predicted by our models appear in the fly connectome, and preliminary results suggest possible cell-intrinsic activity-dependent compensation in Kenyon cells. Our results suggest that homeostatic plasticity and compensatory variability help maintain sparse coding for odour-specific memories.
Biography:
Andrew Lin graduated from Harvard University before completing his PhD at Cambridge. He became a Postdoctoral Research Fellow at the University of Oxford before taking up a lectureship at the University of Sheffield. The Lin lab look at how the brain represents sensory information to allow it to store unique memories, using the olfactory system of the fruit fly Drosophila melanogaster as a model system.