Time-Resolved Fast Mammalian Behavior Reveals the Complexity of Protective Pain Responses

Liam E. Browne, Alban Latremoliere, Brendan P. Lehnert, Alyssa Grantham, Catherine Ward, Chloe Alexandre, Michael Costigan, Frédéric Michoud, David P. Roberson, David D. Ginty, Clifford J. Woolf

Research output: Contribution to journalArticlepeer-review

Abstract

Potentially harmful stimuli are detected at the skin by nociceptor sensory neurons that drive rapid protective withdrawal reflexes and pain. We set out to define, at a millisecond timescale, the relationship between the activity of these sensory neurons and the resultant behavioral output. Brief optogenetic activation of cutaneous nociceptors was found to activate only a single action potential in each fiber. This minimal input was used to determine high-speed behavioral responses in freely behaving mice. The localized stimulus generated widespread dynamic repositioning and alerting sub-second behaviors whose nature and timing depended on the context of the animal and its position, activity, and alertness. Our findings show that the primary response to injurious stimuli is not limited, fixed, or localized, but is dynamic, and that it involves recruitment and gating of multiple circuits distributed throughout the central nervous system at a sub-second timescale to effectively both alert to the presence of danger and minimize risk of harm.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalCell Reports
Volume20
Issue number1
DOIs
StatePublished - Jul 5 2017

Keywords

  • nociception
  • optogenetics
  • pain
  • quantitative behavior
  • reflexes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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