Physiological Processes
physiological processes
Neuroinflammation in Epilepsy: what have we learned from human brain tissue specimens ?
Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum of genetic and acquired forms of focal epilepsies. Dissecting the cellular and molecular mediators of the pathological immune responses and their convergent and divergent mechanisms, is a major requisite for delineating their role in the establishment of epileptogenic networks. The role of small regulatory molecules involved in the regulation of specific pro- and anti-inflammatory pathways and the crosstalk between neuroinflammation and oxidative stress will be addressed. The observations supporting the activation of both innate and adaptive immune responses in human focal epilepsy will be discussed and elaborated, highlighting specific inflammatory pathways as potential targets for antiepileptic, disease-modifying therapeutic strategies.
Remembering Immunity, Central regulation of peripheral immune processes
Thoughts and emotions can impact physiology. This connection is evident by the emergence of disease following stress, psychosomatic disorders, or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. In this talk, I will focus on the brain’s involvement in regulating the peripheral immune response and explore the question of how the brain evaluates and represents the state of the immune system it regulates.
Integration of „environmental“ information in the neuronal epigenome
The inhibitory actions of the heterogeneous collection of GABAergic interneurons tremendously influence cortical information processing, which is reflected by diseases like autism, epilepsy and schizophrenia that involve defects in cortical inhibition. Apart from the regulation of physiological processes like synaptic transmission, proper interneuron function also relies on their correct development. Hence, decrypting regulatory networks that direct proper cortical interneuron development as well as adult functionality is of great interest, as this helps to identify critical events implicated in the etiology of the aforementioned diseases. Thereby, extrinsic factors modulate these processes and act on cell- and stage-specific transcriptional programs. Herein, epigenetic mechanisms of gene regulation, like DNA methylation executed by DNA methyltransferases (DNMTs), histone modifications and non-coding RNAs, call increasing attention in integrating “environmental information” in our genome and sculpting physiological processes in the brain relevant for human mental health. Several studies associate altered expression levels and function of the DNA methyltransferase 1 (DNMT1) in subsets of embryonic and adult cortical interneurons in patients diagnosed with schizophrenia. Although accumulating evidence supports the relevance of epigenetic signatures for instructing cell type-specific development, only very little is known about their functional implications in discrete developmental processes and in subtype-specific maturation of cortical interneurons. Similarly, little is known about the role of DNMT1 in regulating adult interneurons functionality. This talk will provide an overview about newly identified and roles DNMT1 has in orchestrating cortical interneuron development and adult function. Further, this talk will report about the implications of lncRNAs in mediating site-specific DNA methylation in response to discrete external stimuli.
Why we all need a good night’s sleep
We seek to determine how circadian rhythms and sleep are integrated with physiological processes to provide optimal fitness and health. Using initially a Drosophila model, and more recently also mammalian models, we have found that aspects of the blood brain barrier (BBB) are controlled by the circadian clock. BBB properties are also influenced by sleep:wake state in Drosophila, and, in fact, appear to be contribute to functions of sleep. This and other work, which implicates sleep in the regulation of metabolic processes, is providing insights into sleep function
BrainGlobe: a Python ecosystem for computational (neuro)anatomy
Neuroscientists routinely perform experiments aimed at recording or manipulating neural activity, uncovering physiological processes underlying brain function or elucidating aspects of brain anatomy. Understanding how the brain generates behaviour ultimately depends on merging the results of these experiments into a unified picture of brain anatomy and function. We present BrainGlobe, a new initiative aimed at developing common Python tools for computational neuroanatomy. These include cellfinder for fast, accurate cell detection in whole-brain microscopy images, brainreg for aligning images to a reference atlas, and brainrender for visualisation of anatomically registered data. These software packages are developed around the BrainGlobe Atlas API. This API provides a common Python interface to download and interact with reference brain atlases from multiple species (including human, mouse and larval zebrafish). This allows software to be developed agnostic to the atlas and species, increasing adoption and interoperability of software tools in neuroscience.
Neuroscience in the mud: interplay between lab and field research for understanding animal behavior
Investigations of the neurophysiological processes underlying animal behaviors are almost exclusively done inside the laboratory, typically using few animal models born and reared under artificially stabilized conditions. Yet, animals living in the wild have to cope with much complex and variable environments. Thus, while the laboratory provides the technical possibilities for physiological research, the field offers a more realistic perspective about the animal´s behavioral abilities. We study neural circuits underlying the visually guided prey and predator behaviors in a semiterrestrial crab. By combining lab and field experiments we have, for example, found that the level of predation risk experienced by the animals in the wild affects the responsiveness of identified neurons involved in the animal escape response. Using this and other results from my lab I will illustrate and discuss the importance of complementing lab with field studies in wild animals for understanding the neural mechanisms subserving behavior.
Tools for Analyzing and Repairing the Brain. (Simultaneous translation to Spanish)
To enable the understanding and repair of complex biological systems, such as the brain, we are creating novel optical tools that enable molecular-resolution maps of such systems, as well as technologies for observing and controlling high-speed physiological dynamics in such systems. First, we have developed a method for imaging specimens with nanoscale precision, by embedding them in a swellable polymer, homogenizing their mechanical properties, and exposing them to water – which causes them to expand manyfold isotropically. This method, which we call expansion microscopy (ExM), enables ordinary microscopes to do nanoscale imaging, in a multiplexed fashion – important, for example, for brain mapping. Second, we have developed a set of genetically-encoded reagents, known as optogenetic tools, that when expressed in specific neurons, enable their electrical activities to be precisely driven or silenced in response to millisecond timescale pulses of light. Finally, we are designing, and evolving, novel reagents, such as fluorescent voltage indicators and somatically targeted calcium indicators, to enable the imaging of fast physiological processes in 3-D with millisecond precision. In this way we aim to enable the systematic mapping, control, and dynamical observation of complex biological systems like the brain. The talk will be simultaneously interpreted English-Spanish) by the Interpreter, Mg. Lourdes Martino. Para permitir la comprensión y reparación de sistemas biológicos complejos, como el cerebro, estamos creando herramientas ópticas novedosas que permiten crear mapas de resolución molecular de dichos sistemas, así como tecnologías para observar y controlar la dinámica fisiológica de alta velocidad en dichos sistemas. Primero, hemos desarrollado un método para obtener imágenes de muestras con precisión a nanoescala, incrustándolas en un polímero hinchable, homogeneizando sus propiedades mecánicas y exponiéndolas al agua, lo que hace que se expandan muchas veces isotrópicamente. Este método, que llamamos microscopía de expansión (ExM), permite que los microscopios ordinarios obtengan imágenes a nanoescala, de forma multiplexada, lo que es importante, por ejemplo, para el mapeo cerebral. En segundo lugar, hemos desarrollado un conjunto de reactivos codificados genéticamente, conocidos como herramientas optogenéticas, que cuando se expresan en neuronas específicas, permiten que sus actividades eléctricas sean activadas o silenciadas con precisión en respuesta a pulsos de luz en una escala de tiempo de milisegundos. Finalmente, estamos diseñando y desarrollando reactivos novedosos, como indicadores de voltaje fluorescentes e indicadores de calcio dirigidos somáticamente, para permitir la obtención de imágenes de procesos fisiológicos rápidos en 3-D con precisión de milisegundos. De esta manera, nuestro objetivo es permitir el mapeo sistemático, el control y la observación dinámica de sistemas biológicos complejos como el cerebro. La conferencia será traducida simultáneamente al español por la intérprete Mg. Lourdes Martino.