Project A09

Descending control of spinal circuits in health and disease

©bestber; Shutterstock

Motor command signals travel from the cortex to the spinal cord via multiple pathways. Cortical neurons are organized in layers (upper left inset, from Dudanova lab), with L2/3 neurons indirectly projecting to the spinal cord (bottom left inset, from Gatto lab) via striatal and brainstem circuits, and L5 neurons making direct synaptic connections. To understand how these pathways cooperate to drive planning and execution of movement, we will functionally map their anatomy, connectivity and activity. “Figure adapted from Dudanova and Gatto lab, unpublished data”

Project A09 investigates the corticospinal neural underpinnings of locomotion in physiological and pathological states. Using mouse as model organism, and leveraging our complementary expertise in circuit and molecular neuroscience, we will assess the dynamics of cortical (Dudanova) and spinal (Gatto) neurons and their interactions in the planning and execution of behaviour. We will undertake a holistic approach, combining cell type-specific in vivo calcium imaging, anatomical mapping, chemogenetic manipulations, and behavioural analyses to elucidate the connectivity and functions of distinct neural pathways, and their alterations in Huntington’s disease. Project A09 will advance our understanding of descending control of spinal locomotor circuits in health and disease.

Project related publications

Motor command signals travel from the cortex to the spinal cord via multiple pathways. Cortical neurons are organized in layers (upper right inset, from Dudanova lab), with L2/3 neurons indirectly projecting to the spinal cord (bottom right inset, from Gatto lab) via striatal and brainstem circuits, and L5 neurons making direct synaptic connections. To understand how these pathways cooperate to drive planning and execution of movement, we will map their anatomy, connectivity and activity.