A Unique Midbrain-Mediated Global Motor Arrest -Upstream and Downstream Circuits of Chx10-PPN Neurons-

• Applicant: Dr. Stephan Dietrich
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536953619

Locomotion is an essential and conserved movement that allows humans and animals to interact with their surroundings. Although locomotion appears seemingly effortless, it is an intricate motor behavior that requires the orchestration of several supraspinal and spinal neuronal substrates activating many axial and limb muscles. Thus, enabling organisms to navigate through and adapt to their environment. Such context-dependent and episodic locomotor behaviors require an interruption or arrest to adjust the movement toward the aimed goal. However, the neural pathways of motor arrest behaviors upon salient environmental changes and aside from fear-related and defensive contexts, are poorly understood. Recently, Goni-Erro H. et al., 2023 showed that optogenetic activation of glutamatergic neurons in the rostral pedunculopontine nucleus (PPN) expressing Chx10 evokes a unique whole-body motor arrest distinct from fear-induced freezing. However, the underlying neuronal pathways, mechanisms, and physiologically relevant environmental cues of the described motor arrest behavior are unknown. The proposed research program aims to elucidate the basic circuitry architecture and underlying mechanisms of the Chx10-PPN neuron-mediated global motor arrest, providing significant insights into how the nervous system orchestrates the precise execution of context-dependent motor actions. Chx10-PPN neurons offer an excellent entry point due to their location at the intersection of processing supraspinal and executing spinal circuits and genetic accessibility. I will examine the Chx10-PPN input neurons and their functional involvement in the unique global motor arrest by utilizing neuroanatomical and optogenetic approaches. The functional significance of distinct input structures will be further used to determine the sensory cues evoking such an arrest behavior, providing first insights into its biological relevance. Furthermore, I will investigate the neuronal downstream actors in the lower brainstem and their functional contribution to the unique global motor arrest. This will be achieved by combining anterograde tracing methods and chemogenetic manipulation of downstream targets during the optically evoked motor arrest. The proposed study will provide essential insights into the neuronal mechanism of context-dependent motor behaviors and link those motor outputs to cellular activities, advancing our understanding of how the nervous system orchestrates complex motor actions.

• DFG Programme: WBP Fellowship
• International Connection: Denmark
• Host: Professor Dr. Ole Kiehn