INPUT AND OUTPUT CONNECTIVITY MATRIX OF CHX10-PPN NEURONS INVOLVED IN PAUSE-AND-PLAY BEHAVIOR

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 to activate many axial and limb muscles. This enables organisms to navigate through and adapt to their environment. Such context-dependent and episodic locomotor behaviors necessitate an interruption or arrest to adjust the movement toward a specific goal. However, the neural pathways for motor arrest behaviors in response to significant environmental changes—beyond fear-related and defensive contexts—are poorly understood. Recently, Goñi-Erro H. et al., Nat Neurosci, 2023, discovered a population of glutamatergic neurons in the rostral pedunculopontine nucleus (PPN) expressing Chx10, which evokes a unique whole-body motor arrest, characterized by a pause-and-play behavior as well as apnea and bradycardia. However, the functional involvement of upstream and downstream brain areas to the described behavior remains largely unknown. To reveal this, we first took advantage of recent rabies virus-based monosynaptic tracing tools and identified distinct presynaptic input neurons to Chx10-PPN neurons in prefrontal areas, hypothalamus, and subthalamus. Second, we used anterograde and retrograde tracing to identify postsynaptic neurons predominantly in the caudal brainstem and assessed their functional involvement in the motor arrest. Together, this work provides insights into the neuronal mechanisms governing context-dependent selection of arresting motor behaviors, linking those motor outputs to cellular activities and advancing our understanding of how the nervous system orchestrates complex motor actions.