Aktivität und Funktion von Bein-Motoneuronen in laufenden Drosophila
Zusammenfassung der Projektergebnisse
Understanding how neural circuits control arm and leg movements is a major challenge in neuroscience with implications for treating movement disorders, designing neural prostheses, and robotics. Arm and leg movements are driven by motor neurons in the spinal cord (in vertebrates) or ventral nerve cord (in invertebrates). The goal of this research project was to better understand how individual motor neurons are recruited to meet the specific demands of a motor task and to what extent their recruitment relies on sensory feedback. As a DFG postdoctoral fellow in the Tuthill lab at the University of Washington in Seattle, I studied these questions in the fruit fly (Drosophila melanogaster). Fruit flies coordinate their legs in a flexible manner similarly to mammals. The critical advantages of flies are their tractable nervous system and our ability to genetically target specific subsets of neurons. In this research project, I developed a setup for simultaneous two-photon calcium imaging of neural activity in the ventral nerve cord and automated markerless tracking of body and leg movements of tethered flies moving naturally on a spherical treadmill. Using this setup, I first investigated the relationship between leg kinematics and calcium activity in motor neurons during walking. As proposed, I focused on a set of motor neurons that control the movement of the tibia. These motor neurons had previously been characterized in the Tuthill lab in a reduced preparation. I was able to record from these motor neurons in behaving flies, but changes in intracellular calcium did not reveal any obvious, context-dependent differences in their recruitment. Therefore, I focused on the role of sensory feedback in tuning motor neuron activity. Using the same setup as above, I recorded the axon terminals of sensory neurons that provide direct and indirect input to the motor neurons of interest. Specifically, I focused on proprioceptive sensory neurons that signal the position and movement of the tibia. These sensory neurons had previously been characterized in the Tuthill lab in a reduced preparation in response to passive, imposed leg movements. To identify whether they are modulated in a context-dependent manner, I compared my measurements during self-generated leg movements with predictions from computational models that reproduced sensory neuron responses to imposed leg movements. I found that position-encoding sensory neurons were active across behaviors as predicted, whereas particular movement-encoding sensory neurons were much less active during walking and grooming. Using circuit reconstruction in an electron microscopy volume of the Drosophila ventral nerve cord, I found that the sensory neurons receive distinct presynaptic input, suggesting that synaptic release from their axons may be independently modulated. We propose that the function of this modulation could be to suppress expected proprioceptive feedback caused by the fly’s own movement to increase sensitivity to unexpected external perturbations.
Projektbezogene Publikationen (Auswahl)
- (2021). A leg to stand on: computational models of proprioception. Current Opinion in Physiology 22, 100426
Dallmann CJ, Karashchuk P, Brunton B, Tuthill JC
(Siehe online unter https://doi.org/10.1016/j.cophys.2021.03.001) - (2021). Proprioceptive coding of natural leg movements in Drosophila. Conference abstract. CSHL Neurobiology of Drosophila Meeting 2021 (virtual)
Dallmann CJ, Tuthill JC
- (2022). A feedback model for predicting targeted perturbations of proprioceptors during fly walking. Conference abstract. COSYNE 2022, Lisbon, Portugal
Karashchuk P, Walling-Bell S, Dallmann CJ, Brunton B, Tuthill JC
- (2023). Context-dependent modulation of leg proprioception in Drosophila. Conference abstract. Society for Integrative and Comparative Biology Annual Meeting, Austin, TX
Dallmann CJ, Tuthill JC
