Presynaptic inhibition of primary afferents by depolarization: Observations supporting nontraditional mechanisms

Shawn Hochman, Jacob Shreckengost, Hiroshi Kimura, Jorge Quevedo

Research output: Chapter in Book/Entry/PoemConference contribution

34 Scopus citations


Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli and is controlled by pre- and postsynaptic inhibitory mechanisms. Presynaptic inhibition (PSI) is probably the more powerful form of inhibitory control in all primary afferent fibers. A major mechanism producing afferent PSI is via a channel-mediated depolarization of their intraspinal terminals, which can be recorded extracellularly as a dorsal root potential (DRP). Based on measures of DRP latency it has been inferred that this primary afferent depolarization (PAD) of low-threshold afferents is mediated by minimally trisynaptic pathways with pharmacologically identified GABAergic interneurons forming last-order axo-axonic synapses onto afferent terminals. There is still no "squeaky clean" evidence of this organization. This paper describes recent and historical work that supports the existence of PAD occurring by more direct pathways and with a complex pharmacology that questions the proprietary role of GABA and GABAA receptors in this process. Cholinergic transmission in particular may contribute significantly to PAD, including via direct release from primary afferents.

Original languageEnglish (US)
Title of host publicationNeurons and Networks in the Spinal Cord
PublisherBlackwell Publishing Inc.
Number of pages13
ISBN (Print)9781573317788
StatePublished - Jun 2010

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • DRP
  • PAD
  • dorsal horn
  • presynaptic inhibition
  • sensory

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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