IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells

In the rat cerebellum, Golgi cells receive serotonin-evoked inputs from Lug aro cells (L-IPSCs), in addition to spontaneous inhibitory inputs (S-IPSCs) . In the present study, we analyze the pharmacology of these IPSCs and show that S-IPSCs are purely GABAergic events occurring at basket and stellate cell synapses, whereas L-IPSCs are mediated by GABA and glycine. Corelease of the two transmitters at Lugaro cell synapses is suggested by the fact th at both GABA(A) and glycine receptors open during individual L-IPSCs. Doubl e immunocytochemical stainings demonstrate that GABAergic and glycinergic m arkers are coexpressed in Lugaro cell axonal varicosities, together with th e mixed vesicular inhibitory amino acid transporter. Lugaro cell varicositi es are found apposed to glycine receptor (GlyR) clusters that are localized on Golgi cell dendrites and participate in postsynaptic complexes containi ng GABA(A) receptors (GABA(A)Rs) and the anchoring protein gephyrin. GABA(A )R and GlyR/gephyrin appear to form segregated clusters within individual p ostsynaptic loci. Basket and stellate cell varicosities do not face GlyR cl usters. For the first time the characteristics of GABA and glycine cotransm ission are compared with those of GABAergic transmission at identified inhi bitory synapses converging onto the same postsynaptic neuron. The ratio of the decay times of L-IPSCs and of S-IPSCs is a constant value among Golgi c ells. This indicates that, despite a high cell-to-cell variability of the o verall IPSC decay kinetics, postsynaptic Golgi cells coregulate the kinetic s of their two main inhibitory inputs. The glycinergic component of L-IPSCs is responsible for their slower decay, suggesting that glycinergic transmi ssion plays a role in tuning the IPSC kinetics in neuronal networks.