c-Maf expressing spinal interneurons are part of a dorsal horn circuit that integrates descending input from the cortex with peripheral sensory signals.

Aims

Interneurons in the deep dorsal horn of the spinal cord receive input mainly from non-nociceptive myelinated sensory fibers and are believed to be important for the processing of touch and proprioceptive input. There is also accumulating evidence that under certain pathogenic conditions such as neuropathy, deep dorsal horn excitatory interneurons gain access to pain processing circuits. However, detailed analysis of the effect these interneurons exert on pain signaling in naïve or neuropathic mice is lacking.

Methods

Here we use the gene coding for the transcription factor c-Maf as a genetic marker to gain access to spinal interneurons in laminae III-IV. We used intersectional genetic targeting approaches to manipulate the activity of c-Maf interneuron populations and analyze their circuit integration.

Results

We found that, in the adult, c-Maf is expressed by a heterogeneous population of dorsal horn interneurons. Activation of excitatory c-Maf neurons or inhibition of inhibitory c-Maf neurons led to mechanical hypersensitivity. Conversely, loss of function experiments indicated that excitatory c-Maf neurons are dispensable for pain perception in naïve mice but relevant for the detection of noxious touch in neuropathic mice. We also demonstrate that c-Maf interneurons receive direct synaptic input from both low-threshold mechanical receptors (LTMRs) and corticospinal neurons.

Conclusions

We have identified a population of deep dorsal horn interneurons that integrates descending inputs from the cortex with peripheral sensory signals to modulate the perception of sensory stimuli. Excitatory c-Maf neurons appear to be part of an altered circuit that detects noxious touch in neuropathic mice.