Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior

Neuron. 2019 Apr 17;102(2):420-434.e8. doi: 10.1016/j.neuron.2019.02.002. Epub 2019 Feb 27.


Presynaptic inhibition (PSI) of primary sensory neurons is implicated in controlling gain and acuity in sensory systems. Here, we define circuit mechanisms and functions of PSI of cutaneous somatosensory neuron inputs to the spinal cord. We observed that PSI can be evoked by different sensory neuron populations and mediated through at least two distinct dorsal horn circuit mechanisms. Low-threshold cutaneous afferents evoke a GABAA-receptor-dependent form of PSI that inhibits similar afferent subtypes, whereas small-diameter afferents predominantly evoke an NMDA-receptor-dependent form of PSI that inhibits large-diameter fibers. Behaviorally, loss of either GABAA receptors (GABAARs) or NMDA receptors (NMDARs) in primary afferents leads to tactile hypersensitivity across skin types, and loss of GABAARs, but not NMDARs, leads to impaired texture discrimination. Post-weaning age loss of either GABAARs or NMDARs in somatosensory neurons causes systemic behavioral abnormalities, revealing critical roles of two distinct modes of PSI of somatosensory afferents in adolescence and throughout adulthood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Behavior, Animal*
  • Bicuculline / analogs & derivatives
  • Bicuculline / pharmacology
  • Discrimination, Psychological
  • GABA-A Receptor Antagonists / pharmacology
  • Hyperesthesia / genetics
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neural Inhibition*
  • Neurons, Afferent / metabolism
  • Presynaptic Terminals / metabolism*
  • Pyridazines / pharmacology
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sensory Receptor Cells / metabolism*
  • Skin / innervation*
  • Spinal Cord Dorsal Horn
  • Touch*


  • GABA-A Receptor Antagonists
  • Gabrb3 protein, mouse
  • Gprin1 protein, mouse
  • Nerve Tissue Proteins
  • Pyridazines
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • gabazine
  • bicuculline methochloride
  • Bicuculline