Integrated input-output connectomics at single-neuron resolution reveals parallel projection streams in the mouse...

The ventral posterolateral nucleus (VPL) has long been regarded as a linear relay of somatosensory information from the spinal cord to the primary somatosensory cortex (SSp). However, the circuit architecture underlying VPL integration of non-sensory signals, including motor commands and affective states, remains poorly defined; in particular, the relevant circuit mechanisms of canonical excitatory neurons labeled by vesicular glutamate transporter 2 (VGluT2) within this nucleus remain largely unelucidated. By combining monosynaptic rabies tracing with fluorescence micro-optical sectioning tomography (fMOST), we generated a quantitative, single-cell resolution connectome of VPL^VGluT2 neurons in mice. We find that these neurons receive substantial convergent inputs from motor, limbic, and basal ganglia circuits, challenging the classical view that VPL is a unimodal sensory relay. Single-neuron reconstructions (n = 149) further reveal four distinct projection subtypes that innervate not only the SSp but also the primary motor cortex (MOp) and higher-order association areas. Notably, projections to MOp preferentially target layer 5, bypassing the canonical sensory hierarchy. These anatomical findings are consistent with the hypothesis that the VPL may serve as a hub for sensorimotor integration, and they provide a critical structural basis for understanding how somatosensation interfaces with action and cognition.