SFB 1451:  Key mechanisms of motor control in health and disease

Understanding the mechanisms underlying motor control is pivotal, as the motor system governs all interactions with the environment. Motor activities range from monosynaptic reflexes to complex behavior, relying on an interplay of neurons and muscles. If successful, motor control allows us to act in a coordinated and meaningful way, ensuring our bodies’ stability and integrity. Motor control is flexible, allowing constant adaptation, shaped across the lifespan, and disturbed in many neuropsychiatric diseases. It is implemented at different anatomical levels through molecular, cellular, and system processes, maximizing the complexity of how motor control is enabled, maintained, and adapted. Acknowledging this complexity, CRC 1451 brings together basic and clinician neuroscientists studying molecular, cellular, and system levels in fruit flies, mice, monkeys, and humans. Unlike sensory, cognitive, or affective-emotional processes, motor output is quantifiable and comparable across species. When studying the neural mechanisms underlying motor control, this joint readout helps overcome the grand challenge of neuroscience to bridge molecular, cellular, and system levels. Based on a conceptual framework of motor control developed in the 1st funding period (FP) that allows a unified approach across levels and species, we will extend our cross-species investigations of locomotor, dexterous, and adaptive motor control mechanisms in the 2nd FP. CRC 1451 is structured along three highly interactive research areas, accounting for the described complexity. After identifying relevant motor control components in the 1st FP, the projects of Research Area A (Identifying critical genes, molecules, and networks) will now advance our understanding of how molecules, cells, and networks interact during voluntary movements. Research Area B (Key mechanisms of motor control across the lifespan) will extend its work by assessing at multiple levels how adaptation is enabled and how it contributes to the maturation of motor control and its plasticity in neurodegenerative diseases or stroke. The projects of Research Area C (Motor control (dys-)function in neuropsychiatric disorders) will continue exploring motor control dysfunction using neuropsychiatric disorders as “lesion models” but extend the 1st FP’s findings by pursuing the newly developed theme of state-dependent motor control. The service projects Z02, Z03, and INF contribute essentially to the CRC 1451 research program, enabling extensive behavioral assessments that we will compare across species through standardized data collection, analysis, and modeling. We will pursue our endeavor to develop a comprehensive cross-species motor control model covering multiple levels by the end of the maximum CRC 1451 funding period. A more thorough understanding of motor control will further our understanding of neuropsychiatric disorders affecting the motor system, eventually opening new vistas for disease-modifying therapie.

DFG Programme Collaborative Research Centres

International Connection Israel

• A02 - The role of the autophagy-endolysosome system in Purkinje cell survival and the impact of its dysfunction on brain-wide motor circuits (Project Heads Kononenko, Natalia ;  Liebscher, Sabine )
• A04 - The role of hypothalamic and reward-processing neuronal circuits in adaptive regulation of motor behaviors in maternal mice (Project Heads Korotkova, Tatiana ;  Petzold, Anne ;  Valtcheva, Silvana )
• A05 - Neuronal mechanisms underlying motor flexibility in fruit fly walking (Project Heads Büschges, Ansgar ;  Ito, Kei )
• A06 - Role of subcortical signals in selecting and updating motor plans (Project Heads Nawrot, Martin Paul ;  Prut, Yifat )
• A08 - Microglia-mediated regulation of striatal neuronal activity and motor control – mechanisms and functions (Project Heads Korotkova, Tatiana ;  Schaefer, Anne ;  Vay, Sabine )
• A09 - Descending control of spinal circuits in health and disease (Project Heads Dudanova, Ph.D., Irina ;  Gatto, Ph.D., Graziana )
• B01 - Molecular and cellular mechanisms of persistent cortico-striatal motor dysfunction in mouse models of neurodevelopment disorders (Project Heads Isbrandt, Dirk ;  Roeper, Jochen )
• B02 - Complex motor skills in children and adolescents: maturational trajectories and developmental disorders (Project Heads Bender, Stephan ;  Konrad, Kerstin )
• B03 - Modeling neural network dynamics underlying motor control in health and disease (Project Heads Daun, Silvia ;  Fink, Gereon Rudolf )
• B05 - Identification of overarching components in neuromotor phenotypes (Project Heads Eickhoff, Simon ;  Genon, Ph.D., Sarah )
• B06 - Network-level mechanisms underlying adaptation of motor control (Project Heads Fink, Gereon Rudolf ;  Volz, Lukas Jan )
• C01 - Repetitive tDCS in a mouse model of internal capsule stroke: effects on white matter, motor control, plasticity, and recovery of function (Project Heads Aswendt, Markus ;  Rüger, Maria Adele )
• C03 - Striatales Dopamin und motorische Kontrolle: Einfluss körperlicher Zustände auf die Motivation motorischer Anstrengung (Project Heads van Eimeren, Thilo ;  Hönig, Ph.D., Merle )
• C04 - Gait disturbances in neurodegenerative diseases: A window into the interaction between the motor system and cognition (Project Heads Barbe, Michael ;  Drzezga, Alexander ;  Weiss-Blankenhorn, Peter )
• C05 - The role of sensorimotor integration for motor control in the lesioned brain (Project Heads Grefkes-Hermann, Christian ;  Tscherpel, Caroline )
• C06 - Circuit mechanisms interfacing adaptive motivation and motor control — Depression as a model of reversible motor control impairment (Project Heads Jessen, Frank ;  Tittgemeyer, Marc )
• C07 - The role of thalamic and subthalamic nuclei in action planning and adaptation in hypo- and hyperkinetic motor disorders (Project Heads Dembek, Till Anselm ;  Petry-Schmelzer, Jan Niklas ;  Visser-Vandewalle, Ph.D., Veerle )
• C08 - Synaptic Lipid Signaling: Impact on psychomotor control (Project Heads Nitsch, Robert ;  Vogt, Johannes )
• INF - Data management for reproducible data-driven computational modeling cross-species and cross-labs (Project Heads Daun, Silvia ;  Hanke, Michael ;  Nawrot, Martin Paul )
• MGK - Integrated Research Training Group (“MotoRTG”) (Project Heads Büschges, Ansgar ;  Korotkova, Tatiana )
• Z01 - Central Office (Project Head Fink, Gereon Rudolf )
• Z02 - Animal Motor Circuits Core Facility (Project Heads Büschges, Ansgar ;  Gatto, Ph.D., Graziana ;  Korotkova, Tatiana )
• Z03 - Human Motor Assessment Center (Project Heads Fink, Gereon Rudolf ;  Grefkes-Hermann, Christian ;  Jost, Stefanie ;  Weiss-Blankenhorn, Peter )

• A01 - Understanding plastin 3 and its interactors in motor neuron function and plasticity in health and disease (Project Heads Kloppenburg, Peter ;  Wirth, Brunhilde )
• A03 - The role of the reward system in obesity- and ageing-associated changes of motor behaviours (Project Head Korotkova, Tatiana )
• A07 - Role of synaptic lipid modulated cortical excitability in motor control (Project Heads Nitsch, Robert ;  Vogt, Johannes )
• B04 - Motor control under uncertainty in the healthy human brain (Project Heads Mengotti, Paola ;  Vossel, Simone )

Applicant Institution Universität zu Köln

Participating University Goethe-Universität Frankfurt am Main; Hebrew University of Jerusalem
The Paul Baerwald School of Social Work & Social Welfare; Universität Münster

Participating Institution Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE); Forschungszentrum Jülich; Max-Planck-Institut für Biologie des Alterns; Max-Planck-Institut für Stoffwechselforschung

Spokesperson Professor Dr. Gereon Rudolf Fink