Identifying local and descending inputs for primary sensory neurons
Yi Zhang, … , Xiang Zhou, Fan Wang
Yi Zhang, … , Xiang Zhou, Fan Wang
Published August 31, 2015
Citation Information: J Clin Invest. 2015;125(10):3782-3794. https://doi.org/10.1172/JCI81156.
View: Text | PDF
Research Article Neuroscience

Identifying local and descending inputs for primary sensory neurons

Abstract

Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses–based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM). The viral-traced central neurons were largely inhibitory but also consisted of some glutamatergic neurons in the spinal cord and serotonergic neurons in the RVM. The majority of RVM-derived descending inputs were dual GABAergic and enkephalinergic (opioidergic). These inputs projected through the dorsolateral funiculus and primarily innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons in adult animals substantially increased or decreased behavioral sensitivity, respectively, to heat and mechanical stimuli. These results are consistent with the fact that both GABA and enkephalin can exert presynaptic inhibition of the sensory afferents. Taken together, this work provides a systematic view of and a set of tools for examining peri- and extrasynaptic regulations of pain-afferent transmission.

Authors

Yi Zhang, Shengli Zhao, Erica Rodriguez, Jun Takatoh, Bao-Xia Han, Xiang Zhou, Fan Wang

×

Figure 1

Schematic drawing of strategy for tracing presynaptic inputs onto sensory afferents.

Options: View larger image (or click on image) Download as PowerPoint
Schematic drawing of strategy for tracing presynaptic inputs onto sensor...
(A) Genetic crosses were used to generate Avil-Cre RΦGT and Trpv1-Cre RΦGT mice such that the rabies G protein can be selectively expressed in either all or TRPV1-lineage of DRG sensory neurons. (B) ΔG-RV-GFP was injected into the plantar skin of the right front paw of P1 pups, as illustrated. Seven days after injection, the samples are collected and analyzed. (C) Expected outcome of the viral tracing experiments: ΔG-RV-GFP will infect DRG neurons from peripheral axon terminal and will be transported back to the cell bodies, where the deficient virus will be complemented by the rabies G protein. Subsequently, some of the replicated ΔG-RV-GFP will be released at the central afferent terminals in the dorsal horn and infect their putative presynaptic partners.