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Modulation of sensory processing by direct descending projections from the somatosensory cortex to the spinal dorsal horn

Abstract : Noxious stimuli are sensed by specialized sensory neurons of the peripheral nervous system called nociceptors. The nociceptive information is then processed in the spinal cord dorsal horn, which contains local interneurons and projection neurons that send axons to the brain. Supraspinal areas in turn project downwards to the spinal cord where they contribute to the gating of nociceptive signals. Exaggerated and abnormal pain sensitivity is accompanied by alterations in spinal processing and descending pain control systems. The connection between the somatosensory cortex in particular and the spinal cord is conserved in mammals, but very little is known about its role in modulating spinal sensory processing. A major challenge of studying neuronal circuits is to specifically label and target defined groups or subgroups of neurons. Classical approaches include targeting of genetically defined neuronal populations based on the expression of a marker gene. However, this is not always sufficient to define functionally distinct groups of neurons. Here, we describe and used genetic and viral tageting strategies based on the connectivity pattern of the neurons as well as the expression of one or two marker genes. In particular, we used a combination of transgenic mouse lines and intraspinal and cortical injections of recombinant viral vectors to identify and target specific neurons in the cortex and lumbar spinal cord. We identified a population of pyramidal neurons in the somatosensory cortex that project directly to the spinal dorsal horn (S1-CST neurons). These neurons make direct contacts onto c-maf expressing interneurons in the deep dorsal horn which also receive direct inputs from low threshold mechanosensory primary afferents. Additionnally, pharmacogenetic manipulation of c-maf neurons led to altered processing of mechanical stimuli. These results identify two elements of a circuit that integrates descending inputs from the cortex with peripheral sensory signals and contributes to the modulation of somatosensory perception.
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Noémie Frezel. Modulation of sensory processing by direct descending projections from the somatosensory cortex to the spinal dorsal horn. Neuroscience. Université Paris sciences et lettres; Universität Zürich, 2019. English. ⟨NNT : 2019PSLEE018⟩. ⟨tel-02528239⟩

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