Data for: Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn

Spinally-projecting serotonergic neurons play a key role in controlling
pain sensitivity and can either increase or decrease nociception depending
on physiological context. It is currently unknown how serotonergic neurons
mediate these opposing effects. Utilizing virus-based strategies, we
identified two anatomically separated populations of serotonergic
hindbrain neurons located in the lateral paragigantocellularis (LPGi) and
the medial hindbrain, which respectively innervate the superficial and
deep spinal dorsal horn and have contrasting effects on pain perception.
Our tracing experiments revealed an unexpected high selectivity of
serotonergic neurons of the LPGi for transduction with spinally injected
AAV2retro vectors while medial hindbrain serotonergic neurons were largely
resistant to AAV2retro transduction. Taking advantage of this selectivity,
we employed intersectional chemogenetic approaches to demonstrate that
activation of the LPGi serotonergic projections decreases thermal
sensitivity, whereas activation of medial serotonergic neurons increases
sensitivity to mechanical von Frey stimulation. Together these results
suggest that there are functionally distinct classes of serotonergic
hindbrain neurons that differ in their anatomical location in the
hindbrain, their postsynaptic targets in the spinal cord, and impact on
nociceptive sensitivity. At least the LPGi neurons give rise to rather
global and bilateral projections throughout the rostrocaudal extent of the
spinal cord suggesting that they contribute to widespread systemic pain
control.