Neuron Type-Specific Translatomes in Spinal Cords of Naive and Neuropathic Mice

Abstract

The spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, the molecular identity of the underlying neurons and signaling mechanisms are still only partially understood. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (VGLUT2+) and inhibitory GABA and/or glycinergic (VGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are primarily set apart by the expression of genes encoding transcription factors or genes related to the production, release or re-uptake of their principal neurotransmitters (glutamate, GABA or glycine). Subsequent gene ontology (GO) term analyses revealed that neuropeptide signaling-related GO terms were highly enriched in the excitatory population. Eleven neuropeptide genes displayed largely non-overlapping expression patterns closely adhering to the laminar and hence also functional organization of the spinal cord grey matter, suggesting that they may serve as major determinants of modality-specific processing. Since this modality-specific processing of sensory input is severely compromised in chronic, especially neuropathic, pain, we also investigated whether peripheral nerve damage changes the neuron typespecific translatome. In summary, our results suggest that neuropeptides contribute to modalityspecific sensory processing in the spinal cord but also indicate that altered sensory encoding in neuropathic pain states occurs independent of major translatome changes in the spinal neurons.