Figure 2.

Working model for the molecular and structural reorganization of inhibitory synapses on the cell surface of axotomized motoneurons. Top: normal organization of mixed GABA/glycine synapses on adult motoneurons. Glycine content is higher than GABA in mature synapses on the cell body of motoneurons. Each synaptic bouton forms multiple synaptic complexes (usually >6) and each has a postsynaptic density (PSD) formed by a gephyrin scaffold that co-clusters GABA_A and glycine receptors, with glycine receptors at higher density in mature synapses. Neuroligin-2 interacts with gephyrin and binds presynaptic neurexin located adjacent to the release site or presynaptic active zone (PAZ). The direction of the ionic synaptic current is defined by the chloride concentration gradient maintained low intracellularly by the activity of KCC2. Bottom: after axotomy, neuroligin, gephyrin, and KCC2 are removed. Glycine receptors increase their mobility and internalization is unmatched by new membrane insertion since glycine receptor expression strongly decreases. In contrast, the expression of GABA_A receptors with α2 and β2/3 subunits is maintained. In the presynaptic bouton, there is an increase in GABA synthesis. Bouton size is also reduced and contains fewer synaptic complexes and these now operate with a significant GABAergic component (see references in the text).