Figure 7.

Schematic summary of the ultrastructural and electrophysiological results obtained in this study. (a) Representation of a simplified hypothetical circuit compatible with the ultrastructural findings and electrophysiological recordings from rat laminae III/V neurons. The synaptic organization of the low-threshold A fiber is based on a drawing from Maxwell et al.⁶⁰ showing that functionally identified hair follicle afferents receive axo-axonic synapses forming en passant (1) or terminal (2) boutons. These inhibitory terminals can be recognized as they contain flat or pleomorphic vesicles, form symmetric contacts and are immunoreactive for GABA/glycine. The GABA_B2 subunit is not expressed at these synapses but at the axo-dendritic glutamatergic synapses made by the A fiber onto the laminae III-IV neurons. These synapses are asymmetric and contain round vesicles labeled with the anti-glutamate antiserum. For simplicity, we have represented four synapses made by the same fiber impinging onto a patch-clamped laminae III-IV neuron. This recalls the results of quantitative analysis of immunogold labeling (see text). The scheme also takes in account the quantitative TEM data on GABA_B2 subunit-specific localization at the synaptic specializations. The pre and/or postsynaptic localization of GABA_B2 at these synapses is consistent with the results of patch-clamp experiments. For simplicity, we have not considered the possibility that presynaptic GABA_B2 is also expressed by glutamatergic excitatory interneurons and by glutamate-unreactive axons of (presumptive) descending origin. Both possibilities are considered in Discussion section.

(b) to (c): Schematic illustration of the presynaptic modulation mediated by GABA_A and GABA_B receptors expressed on low-threshold A fiber terminals in dorsal horn laminae III/IV. Synaptic activation of GABA_ARs causes the depression of the second EPSC during repetitive stimulation of A fibers (b), while tonic activation of GABA_BRs by local GABA depresses the first response (c). On the right of each panel, example traces of evoked EPSCs showing the effect of presynaptic inhibition exerted by GABA_ARs (blue trace) or GABA_BRs (red trace). GABA: γ-aminobutyric acid; GABA_B2: subunit B2 of the GABA receptor; GABA_AR: GABA_A receptor; GABA_BR: GABA_B receptor.