Developmental dissociation of presynaptic inhibitory neurotransmitter and postsynaptic receptor clustering in the hypoglossal nucleus

At postsynaptic densities of mouse hypoglossal motoneurons, the proportion of glycine receptors co-clustered with GABAA receptors increases from neonatal to adult animals, suggesting that mixed synapses might play a greater role in adult synaptic inhibition. We visualized the presynaptic correlates of these developmental changes using immunocytochemistry. At P5, presynaptic terminals contained glycine and GlyT2 and/or GABA and GAD65, but at P15, the majority of inhibitory terminals contained glycine and GlyT2 only. The GABAergic component of evoked inhibitory postsynaptic currents in HMs decreased strongly between P5 and P15. Similarly, miniature inhibitory postsynaptic currents evolved from mainly glycinergic and mixed glycinergic/GABAergic events at P3–5 to predominantly glycinergic currents at P15. These results indicate that the decrease in the proportion of functional mixed inhibitory synapses with maturation results from a loss of the ability of presynaptic terminals to release both neurotransmitters during development while co-aggregation of GlyRs + GABAARs at postsynaptic loci remained.