Glycinergic and GABAergic tonic inhibition fine tune inhibitory control in regionally distinct subpopulations of dorsal horn neurons.
Inhibition mediated by glycine and GABA in the spinal cord dorsal horn is essential for controlling sensitivity to painful stimuli. Loss of inhibition results in hyperalgesia, a sensitized response to a painful stimulus, and allodynia, a pain-like response to an innocuous stimulus like touch. The latter is due, in part, to disinhibition of an excitatory polysynaptic pathway linking low threshold touch input to pain projection neurons. This critical impact of disinhibition raises the issue of what regulates the activity of inhibitory interneurons in the dorsal horn under non-pathological conditions. We have found that inhibitory neurons throughout lamina I-III, identified by the GAD67 promoter-driven EGFP, are tonically inhibited by glycine or GABA in a regionally distinct way that is mirrored by their inhibitory synaptic input. This tonic inhibition strongly modifies action potential firing properties. Surprisingly, we found that inhibitory neurons at the lamina II/III border are under tonic glycinergic control and receive synapses that are predominantly glycinergic. Futhermore, this tonic glycinergic inhibition remains strong as the mice mature postnatally. Interestingly, GlyT1, the glial glycine transporter, regulates the strength of tonic glycinergic inhibition of these glycine-dominant neurons. The more dorsal lamina I and IIo inhibitory neurons are mainly under control by tonic GABA action and receive synapses that are predominantly GABAergic. Our work supports the hypothesis that tonic glycine inhibition controls the inhibitory circuitry deep in lamina II that is likely to be responsible for separating low threshold input from high threshold output neurons of lamina I.
Takazawa
Tomonori
T
Department of Physiology and Cellular Biophysics, Columbia University, 630 W. 168st St, New York, NY 10032, USA. tt2225@columbia.edu
MacDermott
Amy B
AB
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005998:Glycine / Q000502:physiology*; D050487:Glycine Plasma Membrane Transport Proteins / Q000502:physiology; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D020671:Posterior Horn Cells / Q000254:growth & development / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D050487:Glycine Plasma Membrane Transport Proteins; D005680:gamma-Aminobutyric Acid; D005998:Glycine