Glycine receptor and release site organization impacts the kinetics of glycinergic synapse currents.

Abstract

Glycinergic synapses are the most abundant inhibitory synapses in the brainstem and spinal cord and are important for mediating rhythmic behaviors, such as locomotion and breathing. These synapses present significant variability in sizes and the intrasynaptic nanostructural organization of postsynaptic receptor clusters and presynaptic transmitter release sites. For example, in some cell types glycinergic synapses are comprised of multiple large receptor clusters located at the synapse periphery. Moreover, it has been shown that glycinergic synapses, similarly to other excitatory and inhibitory synapses, can be organized in transsynaptic nanocolumns comprised of presynaptic transmitter release sites precisely aligned opposed to dense postsynaptic receptor nanoclusters. However, while previous work has explored the functional roles of analogous specializations at other synapse types, the functional roles of these structural features have not been explored in glycinergic synapses. Here, we use a Monte Carlo simulation framework (MCell/Blender) to capture synapse structure-function relations in glycinergic synapses. In particular, we model glycinergic synapse currents in synapses containing peripheral receptors and ones comprised of transsynaptic nanocolumns, and compare these with currents in more simply organized synapses. Thus, we discover that the organization of receptors and release sites in glycinergic synapses strongly affects current kinetics, with smaller effects on amplitudes. Specifically, peripheral positioning of receptors makes synaptic currents decay rapidly, while forming transsynaptic nanocolumns gives rise to more sustained currents, where the decay rate decreases with receptor density. Put together, this implies that the formation of transsynaptic nanocolumns is required for large glycinergic synapses with peripherally located receptors to present sustained currents. These effects on the kinetics of glycinergic inhibitory synapse currents are expected, in turn, to shape how excitatory inputs inhibited by these synapses would be integrated by the cell.