Parallel ascending spinal pathways for affective touch and pain

Abstract

The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain1-4. Projection neurons (PNs) of the anterolateral pathway are attractive therapeutic targets for pain treatment because nociceptive signals emanating from the periphery channel through these spinal PNs en route to the brain.However, the organizational logic of the anterolateral pathway remains elusive. Here, we show that two PN populations that express structurally related GPCRs, TACR1 and GPR83, form parallel ascending circuit modules that cooperate to convey tactile, thermal and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons (PBNL).Axons of Tacr1-and Gpr83-expressing spinoparabrachial (SPB) neurons innervate distinct sets of PBNL subnuclei, and strong optogenetic stimulation of their axon terminals induces distinct escape behaviors and autonomic responses. Moreover, Gpr83-expressing SPB neurons are highly sensitive to cutaneous mechanical stimuli and receive strong synaptic inputs from both high-and low-threshold primary mechanosensory neurons. Remarkably, the valence associated with activation of Gpr83-expressing SPB neurons is either positive or negative depending on stimulus intensity. These findings reveal anatomically, physiologically, and functionally distinct SPB tract subdivisions that underlie affective aspects of touch and pain.

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

“…38,63 Despite this, PVIN photostimulation evoked excitatory input in laminae I-IIo, suggesting most of these cells receive PVIN input through ventrally directed dendrites. 14,25,48,73 Our data that lamina I PNs also receive direct PVIN input suggest a similar arrangement of dendritic extensions into the PVIN plexus. This is supported by our recent characterisation of mouse lamina I PNs, demonstrating dendritic arbours extend more ventral than previously appreciated.…”

Ascending neurons convey behavioral state to integrative sensory and action selection centers in the brain

“…In summary, here we have shown that ANs encode high-level behaviors that they convey to distinct integrative sensory and action selection centers in the brain. These findings can accelerate our understanding of how ascending neurons in the mammalian spinal cord influence decision-making in the brain [15, 16, 46, 55–57], and also inspire the development of more effective algorithms for robotic sensory contextualization and action selection [2].…”

Dissecting the Neural Circuitry for Pain Modulation and Chronic Pain: Insights from Optogenetics

“…Along with the improvement of devices and methodology, the application of optogenetics at the spinal level helps elucidate the cellular, molecular, and circuit mechanisms of pain transmission and integration with less tissue damage [22,29]. Second-order sensory neurons expressing Tac1 receptor (Tacr1) and GPCR 83 respond to distinct types of stimulation and innervate distinct sets of neurons in the lateral PBN; optogenetic activation of their axon terminals in the PBN induces distinct escape behaviors and autonomic responses [30]. This study reveals two parallel ascending spinal pathways for pain.…”