Emmy Noether Project: Neural mechanisms enabling context-dependent sensorimotor flexibility

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.

NeuroNex Project: Communication, Coordination & Control in Neuromechanical Systems

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.

https://case.edu/neuronex/

Collaborations

Büschges Lab (University of Cologne)
https://zoologie.uni-koeln.de/en/research-groups-divider/bueschges-group

We are closely collaborating with the Büschges Lab on our C3NS NeuroNex project studying the descending control of locomotion. Currently, Michael Dübbert and Till Bockemühl are helping us put together the latest generation of fly virtual reality arenas (with help from Michael Reiser at Janelia). We are also working on a secret mission to have at least 50% of the Büschges Lab moving to Würzburg by 2022.


Haluk Lacin, PhD (Washington University in St. Louis)
https://profiles.wustl.edu/en/persons/haluk-lacin

We are collaborating with Haluk on a project that involves chewing lots of food (preferably Iskender).


Carlos Ribeiro, PhD (Champalimaud Centre for the Unknown)
https://ribeirolab.org

Carlos and his team are experts in nutrition, and we are collaborating on a project that aims to resolve how sensory inputs converge onto modulatory networks that set and respond to metabolic state changes. The Ribeiro lab is developing and running nifty behavioral experiments for this project, which, combined with our circuits work, help us understand the circuits underlying food-sensing.


Prof. Sabine Fischer (CCTB, Würzburg) and Lorenzo Fontolan, PhD (HHMI, Janelia Research Campus)
https://www.biozentrum.uni-wuerzburg.de/en/cctb/research/supramolecular-and-cellular-simulations/people/fischer-sabine-prof-dr/
https://www.janelia.org/people/lorenzo-fontolan

Sabine and Lorenzo are modeling experts and enthusiasts, who are helping us build theoretical models of the modulatory circuits we are characterizing electrophysiologically.


Prof. Tanja Godenschwege (Florida Atlantic University)
http://biology.fau.edu/directory/godenschwege/index.php

Tanja is a visiting scientist with the lab and together we are working on some nifty molecular signaling pathways.


Prof. Mark Frye (UCLA)
https://www.fryelab.net

The Frye and Ache labs share an interest in modulation of visual sensorimotor pathways, and we’ve recently acquired funding from BaCaTec to help kickstart our joint foray into that world.


Gwyneth M. Card, PhD (HHMI, Janelia Research Campus
https://www.hhmi.org/scientists/gwyneth-card

We are working on characterizing the networks underlying landing responses in Drosophila with Jan’s postdoc advisor, Gwyneth Card. This project is supported by a Janelia visitor project grant.

Dr. Sander Liessem (Postdoc)

Locomotion needs to be adjusted to ever-changing environmental and internal demands. For example, animals need to respond to obstacles or conspecifics in their path and integrate a range of sensory information to navigate them, for instance by walking around the obstacle or waiting for the conspecific to pass. To this end, information from diverse and distinct sensory modalities, such as vision or mechanosensation, is integrated by brain circuits, and converges onto a relatively small population of descending neurons. These “output neurons” of the brain communicate with motor centers in the ventral nerve cord, where they control various behaviors, such as curve walking or stopping, an thus adapt motor programs to cope with changes in the environment. To deliver insights into fundamental principles facilitating this sensorimotor flexibility, Sander is combining various techniques such as whole-cell patch clamp recordings, optogenetics, and behavioral analysis.

After finishing his Bachelor’s thesis at the Max Planck Institute for Neurological Research, Sander pursued his postgraduate studies at the University of Cologne where he qualified for the Fast-Track Masters/Doctoral program. He earned his PhD in neurobiology in Ansgar Büschges’ and Reinhard Predel’s Labs. His thesis focused on the identification and role of neuropeptides in insect motor control.

Rituja Bisen (PhD Student)

Rituja has always been intrigued by the complexity of the brain: How does the state of mind affect our behavior? What are the neural mechanisms underlying decision making? What is the role of the environment in shaping our behavior? To answer some of these questions in her PhD project, Rituja is investigating how sensory inputs and internal states are integrated to shape the activity of neuronal networks in the Drosophila brain. Currently, she is spending most of her time befriending fruit flies and convincing them that it makes absolute sense to expose their brains to her, so that she can access their neurons and perform patch-clamp recordings.

Rituja holds a B.Sc in Biochemistry, Genetics and Biotechnology from Bangalore University, India and an MRes in Tissue Engineering and Regenerative Medicine from the University of Manchester, UK. Later, she moved to Germany to pursue her postgraduate studies and obtained a Masters in Molecular and Developmental Stem Cell Biology from Ruhr University Bochum. She carried out her master‘s thesis titled, “Effect of BAP1 mutations on DNA methylation pattern in human iPSCs” in Dr. Steenpaß’s lab at the Institute of Human Genetics, Essen.

Dr. Jan M. Ache (PI)

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. The Ache Lab for 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.

Photorealistic painting of Jan by the talented (Mar)Tina Held.

Dr. Martina Held (Postdoc)

To initiate and control adaptive, context-dependent behavior instantaneously the brain needs to process and integrate a barrage of inputs from various sources with extremely high speed and accuracy. These inputs include complex, multimodal sensory cues from the environment, such as the visual scenery, or an odor plume, as well as intrinsic feedback about the animal’s state. Intrinsic feedback is mediated, for example, by ascending neurons which provide information about the state of the locomotor system. In order to generate appropriate behavioral responses to all this information impinging on the brain simultaneously, a relatively small number of descending neurons, which elicit and control locomotion responses, receives input from numerous sensory processing neurons. So far, the neuronal pathways underlying this process and their connectivity patterns remain largely unknown.

Therefore, Martina’s main research interest lies in the neuronal translation of sensory input to behavioral output, in particular in internal feedback loops that enable state-dependent responses of the system. By combining visual stimulation with two-photon calcium imaging in behaving fruit flies and optogenetic manipulation techniques, Martina is investigating the neuronal processes in populations of neurons that are involved in multimodal integration. In addition to imaging populations of neurons, she acquires data on the single cell level via patch clamp recordings. Comparing findings from single cells to population data will help us understand the neuronal processes underlying context-dependent action selection. 

Martina holds a BSc. in Biology and an MSc. in Organismic Biology from the University of Marburg. As a PhD student, she moved to Würzburg with the lab of Keram Pfeiffer, where she worked in the Department for neuroethology. During her PhD, Martina spent 10 months at HHMI’s Janelia Research Campus as a visiting scientist. She earned her PhD in neurobiology from the University of Marburg with her thesis focusing on anatomical and physiological investigations of the sky-compass system in honeybees and desert locusts.

Dr. Alex S. Chockley (Postdoc)


Alex’s main research interests lie in how animals select behaviors and movements from the entire repertoire available to them at any time. The neural pathways for all behaviors that an animal can perform are always present, yet the nervous system successfully and reliably “selects” those that are most appropriate given the context. This involves an intricate interplay between sensory information, originating both externally and internally, and the state of the animal. Alex is curious to find which of these myriad, dynamic sensory and state signals are most relevant for the elicitation of certain behaviors and how these signals influence the underlying neuronal circuitry.

A native of the United States, Alex moved to Germany to pursue his graduate education in Neuroscience after receiving his B.S. in Zoology from Michigan State University.  He earned an M.Sc. in neurosciences from the University of Bonn, after which he moved on to do a Ph.D. at the University of Cologne. His dissertation work in the Büschges Lab focused on sensorimotor integration between leg proprioceptive signals and locomotor networks.