An immunocytochemical study of glycine receptor and GABA in laminae I- III of rat spinal dorsal horn

Abstract

In order to provide information about the function of glycine in the superficial three laminae of the rat dorsal horn and the possible coexistence of glycine and GABA at synapses in this region, we have carried out a combined study involving preembedding immunocytochemistry with a monoclonal antibody to the glycine receptor and postembedding immunocytochemistry with antiserum to fixed GABA. Glycine receptor-like immunoreactivity was present at axodendritic and axosomatic synapses in all three laminae, and at dendrodendritic synapses in lamina II. Although axons that formed axoaxonic synapses were often presynaptic at immunoreactive axodendritic synapses (and thus probably contained glycine), the axoaxonic synapses themselves did not show glycine receptor-like immunoreactivity. Many of the profiles that were presynaptic at glycine receptor-immunoreactive synapses showed GABA-like immunoreactivity. These results suggest that glycine acts as a postsynaptic inhibitory transmitter at various types of synapses in laminae I-III, and that it may coexist with GABA at many synapses in this region. However, it appears that while glycine and GABA may both be released at axoaxonic synapses, either glycine does not act as a transmitter at these synapses, or else it acts at an atypical receptor that was not recognized by the antibody used in this study.

Intracisternal or intrathecal glycine, taurine, or muscimol inhibit bicuculline-induced allodynia and thermal hyperalgesia in mice

“…This result is consistent with the finding that glycine and GABA are coreleased from the same interneurons [6] . Because spinal glycine and GABA A receptors are localized on the same postsynaptic membranes [4,5] , this finding suggests that GABA and glycine work together to affect sensory modulation. Furthermore, Todd and colleagues reported that both GABAergic and glycinergic neurons are present in spinal Rexed laminae II-IV and that fibers form axoaxonic synapses on Aβ terminals and on the wide dynamic range neurons [5] .…”

“…However, the acute antagonism of spinal GABA A receptors exhibited by bicuculline produces touch-evoked agitation (allodynia) [3] . GABA and glycine are colocalized in interneurons in spinal laminae I-III [4,5] and are coreleased from the same interneurons [6] . However, taurine binds to glycine receptors in the CNS and functions as a partial agonist of GABA A receptors [7] , inhibiting behaviors evoked by intrathecal N-methyl-D-aspartate (NMDA) or kainate injection [8,9] .…”

Glycine transport inhibitors for the treatment of pain

“…Inhibitory glycinergic neurons and receptors are found throughout the CNS, but are most abundant in the dorsal horn of the spinal cord, particularly in lamina III [9][10][11]. GlyT1, GlyT2…”

“…This is due to a reduction in the activity of the potassium chloride co-transporter (KCC2) [27] that leads to an increase in intracellular chloride, so activation of GABA or glycine receptors causes depolarization and a pronociceptive excitation of these pain transmission neurons. However, GlyT inhibitors would not be expected to strongly exacerbate this pronociceptive adaptation because inhibitory neurotransmission in lamina I of the dorsal horn is predominantly GABAergic [28] and GlyT2 expression is relatively sparse in this region [9][10][11].…”

GABA‐, glycine‐, and glutamate‐immunoreactive bouton profiles in apposition to neurons of the central cervical nucleus in the rat

“…There is evidence for a co-release of glycine and GABA, for example at the Renshaw-motoneuron synapses (e.g., Cullheim and Kellerth, 1981). However, at other synapses (in the dorsal horn, for example) both GABA and glycine can be present in the presynaptic bouton, whereas the postsynaptic profile only exhibits one receptor type (Mitchell et al, 1993). Moreover, electrophysiological recordings in lamina I have provided evidence that even though both transmitters may be released at the synapses, the postsynaptic inhibition is mediated solely by glycine (Chéry and De Koninck, 1999).…”