期刊
CELL REPORTS
卷 22, 期 5, 页码 1105-1114出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.01.004
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资金
- Merit Scholarship Program for Foreign Students (PBEEE) scholarship
- Fonds de Recherche du Quebec Sante - (FRQS) Scholarship
- Australian Postgraduate Award
- National Health and Medical Research Council (NHMRC) Career Development Fellowship [GNT1032364]
- Melbourne Children's Clinician Scientist Fellowship
- Canadian Institutes of Health Research (CIHR) [MOP-97758]
- EJLB Foundation
- Quebec Pain Research Network
- Brain Canada
- Canadian Foundation for Innovation
- W. Garfield Weston Foundation
- Swiss National Science Foundation (SNSF) [156393]
- McGill-Zurich Collaboration grant
- NHMRC Australia [GNT1059666, GNT1126153]
- Victorian Government's Operational Infrastructure Support Program
- Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS)
- University of Zurich
- Australian Disorders of the Corpus Callosum (AusDoCC)
Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of topographic organization of spinal ascending projections in nociceptive topognosis, we generated a conditional knockout mouse lacking expression of the netrin1 receptor DCC in the spinal cord. These mice have an increased number of ipsilateral spinothalamic connections and exhibit aberrant activation of the somatosensory cortex in response to unilateral stimulation. Furthermore, spinal cord-specific Dcc knockout animals displayed mislocalized licking responses to formalin injection, indicating impaired topognosis. Similarly, humans with DCC mutations experience bilateral sensation evoked by unilateral somatosensory stimulation. Collectively, our results constitute functional evidence of the importance of topographic organization of spinofugal connections for nociceptive topognosis.
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