MAPPING THE CONNECTIVITY OF SPINAL CORD PROJECTION NEURONS

Execution and adaptation of behavior depend on dynamic interactions among neuron networks across the peripheral and central nervous systems. As the final checkpoint for motor output and a key relay for sensory input, spinal circuits are a critical hub for sensorimotor integration. Spinal circuits, primarily made of interneurons, also include ascending projection neurons. How these projection neurons are embedded within spinal circuits, their molecular identities and brain targets, remain poorly understood.
Using viral and intersectional genetic strategies, we determined (1) a comprehensive atlas of brain regions receiving spinal and dorsal root ganglia (DRG) ascending projections, (2) the postnatal refinement of these projections, and (3) a spinal atlas of brain area-specific projection neurons. The spinal projectome displays topographic organization and is consolidated during postnatal development. We confirmed established targets such as dorsal column nuclei (DCN), parabrachial nucleus and thalamus, and identified novel targets including the dorsal raphe. Within the DCN, DRG projections primarily innervate the external cuneate, while spinal projections [innervate] the cuneate and gracile nuclei.
Projection density and distribution vary by spinal neuron subtype: dorsal neurons target both sensory- and motor-related brain regions, while ventral populations selectively target motor-related areas. Mapping the brain-region-specific spinal projection neurons revealed that spino-thalamic neurons are predominantly contralateral and concentrated at cervical and lumbar levels, whereas spino-parabrachial neurons are both ipsilateral and contralateral and equally present at all spinal levels.
Our detailed analyses of the spinal ascending projectome provide new insights into how sensorimotor information is relayed to the brain to support adaptive behavior.