Our brain can be viewed as a large-scale network consisting of smaller, interconnected neural circuits. These circuits operate through complex interactions to process signals, such as environmental cues and internal feedback. The primary connections between such networks consist of direct, synaptic interactions between individual neurons. In addition, however, every neuron is subject to modulation via so called neuromodulators, which connect neural networks both locally and over great distances. This modulation can strengthen or weaken synaptic connections and therefore allows connectivity changes within the system. The ability of neural networks to process multiple signals, whether they are synaptic or modulatory, permits flexibility in the nervous system, enabling adaption to ever-changing circumstances.
To gain deeper insight into how this complex though flexible system functions, we need to further our understanding of the multiple layers shaping neural interactions. With its powerful genetic toolkit, the model organism Drosophila melanogaster can be exploited to study synaptic connectivity. This may be achieved by tracing individual neurons and synapses to establish a connectome. However, to fully understand the dynamics and connectivity of neural networks, considering the modulation of neural circuits is equally important. For this reason, Isabella focuses on the modulation of neurosecretory cells in Drosophila melanogaster and how their activity patterns are influenced by other neuromodulators. To this end, Isabella is combining optogenetic tools with calcium imaging and whole-cell patch-clamp recordings. Comparing findings on a single-cell level measured via patch-clamp recording to the populational level dynamics assessed via calcium imaging will contribute to a better understanding of reciprocal modulation as well as systemic neuromodulation.
Isabella holds a B.Sc. in Biotechnology from the Technical University of Berlin, where she focused on addiction behavior in Drosophila during her Bachelor’s Thesis in David Owald’s Lab. Now, she is pursuing her Master’s degree in the Fast Track Program FOKUS Life Sciences at the University of Würzburg, and will complete her Master’s Thesis in the Ache Lab.
Our brains integrate many kinds of sensory information to create the appropriate behavioral output in a wide variety of situations. Sensory systems constantly integrate external and internal cues and relay the information to motor systems to drive behavior. In the human brain, a diverse number of circuits and around 90 billion neurons are responsible for these computations. In flies, like Drosophila melanogaster, with less than one million neurons and a brain the size of a poppy seed, the situation is thought to be simpler. Nevertheless, flies are capable of a range of complex behaviors, including navigation and learning. This complex array of behaviors, the small number of neurons, and the genetic toolkit available in Drosophila make them a great model system for the investigation of sensorimotor pathways controlling specific behaviors.
At present, Aleyna is working on her Master‘s Thesis, in which she is studying the integration of visual and mechanosensory inputs by a descending command-type neuron in Drosophila. To this end, she presents visual stimuli using an LED arena and mechanosensory stimuli via air puffs while performing in vivo whole-cell patch-clamp recordings in behaving flies. Thus, she aims to explore how populations of descending neurons integrate multimodal sensory cues to drive behavior.
Aleyna is from Turkey and she graduated with honors from a B.Sc program in Molecular Biology and Genetics at Bogazici University, Istanbul. She is now doing her M.Sc at the JMU Würzburg in the Graduate School of Life Sciences FOKUS program. Her experience so far also includes electrophysiology and immunohistochemistry in mouse brain slices.
Although the brain contains the essence of what makes us human, we still know very little about the complex processes going on inside of it – we don’t even notice much of the work the brain does for us on a daily basis. One of the reasons why I decided to study biology was because of my fascination with this organ and its secrets. A good approach towards understanding complex processes and systems is to start with less complex systems, try to understand those, and then extrapolate the findings to try and grasp general principles.
Drosophila has proven to be a great model system for understanding brains. Flies have a numerically less complex nervous system than vertebrates but are still capable of producing a broad spectrum of adaptive behavior. Furthermore, Drosophila is an easy-to-handle genetically tractable lab animal which greatly facilitates our research. With the help of this model system, we can dive in and understand a little bit more about what I find to be one of the most fascinating feature of the brain: its flexibility. The brain must adapt to the ever-changing demands of the environment and its own body. Moreover, sensory inputs from the environment and the internal state of the animals must be integrated to select and perform adequate behaviors in different situations. For example, flying to a perceived food source and subsequently feeding. Afterwards, the ingested food must be digested and processed, all of which is controlled by neuronal networks. It would therefore be beneficial if sensory input from the environment, such as an appetitive food odor in case the animal is hungry, would activate signaling cascades to prepare the animal’s digestive system even before it starts feeding.
For my bachelor’s thesis I investigated whether specific sensory inputs lead to anticipatory changes in modulatory brain neurons and, ultimately, behavioral adaptions to different external conditions. After finishing my thesis, I took the opportunity to stay in the lab as a student assistant to continue working on the project, while completing my Master of Science at the University of Würzburg.
Animal behavior needs to be flexible and adaptive to changes in the environment, but behavioral decisions also need to take changing internal demands into account. Environmental factors such as incoming predators can trigger escape behaviors, for example, while internal demands, like hunger, can increase food-searching behavior. To achieve appropriate behavioral selection under various, complex conditions, multiple sensory inputs must be received and integrated by neuronal circuits in the brain in a context-dependent manner.
Stefan is studying this context-dependent integration of sensory stimuli by neural circuits and the resulting behavioral responses. He is focusing on descending neurons, which play a major role in eliciting behaviors by controlling and modulating activity pattens in motor networks of the ventral nerve cord (the analogue to the vertebrate spinal cord). In certain behaviors, such as landing, these neurons are gated by the behavioral state of the fly. If the fly is in a state where landing is inappropriate the neurons controlling landing are decoupled from visual stimuli thereby preventing undesired behavioral responses. To elucidate whether state-dependent modulation of descending neurons is a general mechanism mediating action selection, and how this modulation is achieved, Stefan uses in vivo whole-cell patch clamp recordings combined with optogenetic tools and behavioral analysis.
Stefan holds a B.Sc in Applied Biology from the University of Applied Sciences Bonn Rhein-Sieg and a M.Sc in Life and Medical Sciences from the University Bonn. He did his PhD in the group of Prof. Kittel at the Institute of Animal Physiology. His thesis focused on metabotropic mechanosensation in chordotonal organs of Drosophila larvae.
Tanja is a visiting Professor from Florida Atlantic University. We’re collaborating on a project that investigates the role of G protein-coupled receptors in regulating neuronal activity which, according to Tanja, makes us finally do ‘proper mechanistic neuroscience’. Apart from sharing her expertise on sub-cellular signaling pathways, Tanja helps us push our fly game.
Fathima’s interest lies in studying the neural circuits underlying the plethora of behaviours displayed by animals. She is especially fascinated by how different complex behaviours are adapted to changes in the environment.
The fact that the basic units of the brain are separate, discrete cells was still debatable in the late nineteenth century, although vast advances had already been made in understanding many other physiological aspects of our body. What makes the brain so difficult to decipher is its anatomical and functional complexity. One approach to understanding the functional principles of the organ that determines who we are and how we perceive and interact with the world is to study numerically simpler brains, which are nonetheless capable of producing and controlling complex behaviours.
Currently, Fathima is studying the descending pathways that convey information about the environment from sensory organs and central brain circuits to lower motor centers in flies, with a focus on how these descending pathways control and execute locomotion. At present, she is building different setups and standardizing protocols that will allow her to optogenetically manipulate various descending neurons to study more closely the flexible control of locomotion in flies and she is in absolute awe of it. Once our protocols and setups are established, Fathima’s experiments will help us develop a better understanding of how descending pathways modify and direct the ongoing behaviour.
Fathima hails from the southern part of India. She holds a bachelor’s degree in Botany and Biotechnology from Mahatma Gandhi University, Kerala and a master’s degree in Biotechnology from the Cochin University of Science and Technology. She completed her Master’s thesis with the guidance of Dr. Gaurav Das, National Center for Cell Science (NCCS), Pune. She continued the work at the NCCS with the same group before moving to Würzburg to embark on her PhD project.
P.S: Fathima considers reading literary fiction as her sport and was delighted to find out about the big library on the campus in Würzburg. Recently, she has also re-invented her interest in gaming.
One of the most complicated and intriguing objects known to humanity can be found right inside our own head: the human brain. Despite the fact that humans have been fascinated with their brain for centuries, even simple nervous systems, like those of a worm or a fly, remain beyond our grasp. In the last decades, a huge effort has been made to advance our knowledge about the nervous system, but we are still a long way from being able to claim that we ‘understand’ the brain. Studying the brain remains challenging because the experiments we can carry out with the available techniques focus either on single neurons with a high level of precision, or on larger networks and brain areas at the price of losing information about sub-threshold neuronal dynamics. Unfortunately, most of the functions of the nervous system arise from global network activity, but we cannot record all the neurons with high precision at the same time. In this situation, computational models come to our aid, allowing us to develop an insight into the properties of neural networks at a global level, which are difficult or impossible to measure with empirical approaches. These data can then be exploited to design better experiments and to create new, improved hypotheses about network functions.
Modulatory neurons are key to understanding complex neural networks since they enable flexible, adaptive processing of external sensory cues and internal state signals. Since the complexity of these systems is quite high, Federico’s goal is to develop a computational model to understand how the ensemble of neuromodulators acts together to mediate flexible sensorimotor processing and adjust the metabolism of flies to ever-changing external and internal demands. To this end, Feffo is combining patch-clamp recordings from modulatory neurons and sensorimotor pathways with Hodgkin-Huxley type modeling approaches.
Federico holds a Bachelor’s degree in Natural Sciences and a Master’s degree in Neurobiology from La Sapienza-University of Rome, Italy. He also attended a one-year master course at the Advanced School in Artificial Intelligence (AS-AI) held by the Institute of Cognitive Sciences and Technologies, National Research Council (CNR-ISTC) of Rome. Thus, he acquired the necessary skills to complete his MSc thesis in computational neuroscience under the supervision of Dr. Gianluca Baldassarre in the same institute (CNR-ISTC).
To ensure survival in an ever-changing, complex world, animal behavior needs to be flexible and adaptive. Nervous systems have evolved to enable behavioral responses to a wide variety of sensory stimuli, but the adequate behavioral response to a given stimulus is highly context-dependent, and behavioral or internal states accordingly affect sensorimotor processing. For example, locomotion modulates responses of visual neurons, and hunger increases food-searching behavior and shifts taste preferences. Despite their ubiquitous importance, the neural mechanisms enabling context-dependent sensorimotor flexibility are not well understood. My Emmy Noether research program ‘Neural mechanisms enabling context-dependent sensorimotor flexibility’ aims to discover fundamental principles of motor control, in particular with regard to sensorimotor flexibility, by leveraging the power of neurogenetics, electron microscopy-based circuit reconstruction, and in-vivo patch-clamp recordings in behaving Drosophila.
The Ache Lab is part of a NeuroNex Network with the goal of addressing the foundational question: How do biological nervous systems control and execute interactions with the environment?
Our network, which includes scientists and engineers from ten institutions across the United States, the United Kingdom and Germany, is focusing on Communication, Coordination, and Control in Neuromechanical Systems (C3NS) to develop comprehensive models of sensorimotor control with relationships to the environment, both within individual species, and across the phyla Arthropoda, Mollusca and Chordata.
Together, we seek to create a conceptual modeling framework that can predict control for organisms of different size and speed scales. Through our inter-phylum experimental study of sensorimotor control, we seek to identify convergent or conserved principles to refine and inform this framework. Such a framework will have a tremendous effect on the ability to interpret, and extend the impact of, experimental results across biology and robotics, with future applications to prosthetics.
The Ache Lab will closely collaborate with the Büschges, Ito and Blanke Labs at the University of Cologne and Nick Szczecinski’s Lab at the University of West Virginia to contribute a model of Drosophila motor control to the project. C3NS is led by Roger Quinn at Case Western Reserve University.