Dataset Information

Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons.

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, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. 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 not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

SUBMITTER: Das Gupta RR

PROVIDER: S-EPMC7933427 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons.

Das Gupta Rebecca Rani RR Scheurer Louis L Pelczar Pawel P Wildner Hendrik H Zeilhofer Hanns Ulrich HU

Scientific reports 20210304 1

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, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TR ...[more]

PMID: 33664406

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Project description:The superficial dorsal horn (SDH) of the spinal cord represents the first site of integration between innocuous and noxious somatosensory stimuli. According to gate control theory, diverse populations of excitatory and inhibitory interneurons within the SDH are activated by distinct sensory afferents, and their interplay determines the net nociceptive output projecting to higher pain centers. Although specific SDH cell types are ill defined, numerous classifications schemes find that excitatory and inhibitory neurons fundamentally differ in their morphology, electrophysiology, neuropeptides, and pain-associated plasticity; yet little is known about how these neurons respond over a range of natural innocuous and noxious stimuli. To address this question, we applied an in vivo imaging approach in male mice where the genetically encoded calcium indicator GCaMP6s was expressed either in vGluT2-positive excitatory or vIAAT-positive inhibitory neurons. We found that inhibitory neurons were markedly more sensitive to innocuous touch than excitatory neurons but still responded dynamically over a wide range of noxious mechanical stimuli. Inhibitory neurons were also less sensitive to thermal stimuli than their excitatory counterparts. In a capsaicin model of acute pain sensitization, the responses of excitatory neurons were significantly potentiated to innocuous and noxious mechanical stimuli, whereas inhibitory neural responses were only depressed to noxious stimuli. These in vivo findings show that excitatory and inhibitory SDH neurons diverge considerably in their somatosensory responses and plasticity, as postulated by gate control theory.SIGNIFICANCE STATEMENT Gate control theory posits that opposing spinal excitatory and inhibitory neurons, differently tuned across somatosensory modalities, determine the net nociceptive output to higher pain centers. Little is known about how natural stimuli activate these two neural populations. This study applied an in vivo calcium imaging approach to genetically target these neurons and contrast their responses over a range of innocuous and noxious mechanical and thermal stimuli. Compared with excitatory neurons, we found that inhibitory neurons are more sensitive to innocuous touch and far less sensitive to thermal stimuli. An acute model of pain also revealed that these subtypes undergo divergent mechanosensory plasticity. Our data provide important and novel insights for gate-control inspired models of pain processing.

Dataset Information

Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons.

Publications

Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons.

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