Presynaptic plasticity at two giant auditory synapses in normal and deaf mice

Abstract

Large calyceal synapses are often regarded as simple relay points, built for high-fidelity and high-frequency synaptic transmission and a minimal requirement for synaptic plasticity, but this view is oversimplified. Calyceal synapses can exhibit surprising activity-dependent developmental plasticity. Here we compare basal synaptic transmission and activity-dependent plasticity at two stereotypical calyceal synapses in the auditory pathway, the endbulb and the calyx of Held. Basal synaptic transmission was more powerful at the calyx than the endbulb synapse: the amplitude of evoked AMPA receptor-mediated excitatory postsynaptic currents (eEPSCs) was significantly greater at the calyx, as were the release probability, and the number of release sites. The quantal amplitude was smaller at the calyx, consistent with the smaller amplitude of spontaneous miniature EPSCs at this synapse. High-frequency trains of stimuli revealed that the calyx had a larger readily releasable pool of vesicles (RRP), less tetanic depression and less asynchronous transmitter release. Activity-dependent synaptic plasticity was assessed in congenitally deaf mutant mice (dn/dn). Previously we showed that a lack of synaptic activity in deaf mice increases synaptic strength at the endbulb of Held via presynaptic mechanisms. In contrast, we have now found that deafness does not affect synaptic transmission at the calyx synapse, as eEPSC and mEPSC amplitude, release probability, number of release sites, size of RRP, tetanic depression and asynchronous release were unchanged compared to normal mice. Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse.

Medial Superior Olivary Neurons Receive Surprisingly Few Excitatory and Inhibitory Inputs with Balanced Strength and Short-Term Dynamics

“…Here we describe a balance in MSO neurons between excitatory and inhibitory STP, defined as steady state, kinetics, and recovery from depression. This STP is most likely based on presynaptic factors such as pool depletion (Schneggenburger et al, 1999;Wu and Borst, 1999;Oleskevich et al, 2004;Yang and Xu-Friedman, 2008), Ca 2ϩ current inactivation (Forsythe et al, 1998;Xu and Wu, 2005;Mochida et Xu-Friedman, 2008), since we found no indication of a postsynaptic contribution.…”

“…However, inhibitory vesicles impose a 2-to 3-fold larger conductance than excitatory vesicles, resulting in an equal overall conductance. The conductance imposed by the quantal contents of both inputs is large, comparable to an endbulb-type synapse (Oleskevich et al, 2004;Xu-Friedman and Regehr, 2005). The unusual strength of the inhibitory input speaks to the fundamental importance of inhibition in this circuit (Brand et al, 2002;Pecka et al, 2008).…”

“…We plotted the cumulative peak EPSC (Fig. 3I ), and a linear fit to the steady state was backextrapolated to the y-intercept to estimate the current that would be elicited from the release of all physiologically available and readily releasable vesicles (Schneggenburger et al, 1999;Oleskevich et al, 2004). Since we know for each cell the number of activated fibers and the mean quantal size, we can calculate the average apparent pool of vesicles per fiber by dividing the maximal releasable current by the fiber number and the quantal size.…”

“…3J ). In addition, the average release probability, 0.45 Ϯ 0.03, was estimated from the size of the vesicle pool and the quantal content (Schneggenburger et al, 1999;Oleskevich et al, 2004).…”

The Medial Olivocochlear System Attenuates the Developmental Impact of Early Noise Exposure

“…Redd et al 2000;Lee et al 2003). Subsequent functional assessments have confirmed irregular transmission characteristics (Oleskevich and Walmsley 2002;Oleskevich et al 2004;Manis 2005, 2006).…”