Endbulb synaptic depression within the range of presynaptic spontaneous firing and its impact on the firing reliability of cochlear nucleus bushy neurons

Abstract The majority of auditory nerve fibers exhibit prominent spontaneous activity in the absence of sound. More than half of all auditory nerve fibers in CBA mice have spontaneous firing rates higher than 20 spikes/s, with some fibers exceeding 100 spikes/s. We tested whether and to what extent endbulb synapses are depressed by activity between 10 and 100 Hz, within the spontaneous firing rates of auditory nerve fibers. In contrast to rate-dependent depression seen at rates >100 Hz, we found that the extent of depression was essentially rate-independent (∼35%) between 10 and 100 Hz. Neither cyclothiazide nor γ- d -glutamylglycine altered the rate-independent depression, arguing against receptor desensitization and/or vesicle depletion as major contributors for the depression. When endbulb synaptic transmission was more than half-blocked with the P/Q Ca 2+ channel blocker ω-agatoxin IVA, depression during 25 and 100 Hz trains was significantly attenuated, indicating P/Q Ca 2+ channel inactivation may contribute to low frequency synaptic depression. Following conditioning with a 100 Hz Poisson train, the EPSC paired-pulse ratio was increased, suggesting a reduced release probability. This in turn should reduce subsequent depletion-based synaptic depression at higher activation rates. To probe whether this conditioning of the synapse improves the reliability of postsynaptic responses, we tested the firing reliability of bushy neurons to 200 Hz stimulation after conditioning the endbulb with a 25 Hz or 100 Hz stimulus train. Although immediately following the conditioning train, bushy cells responded to minimal suprathreshold stimulation less reliably, the firing reliability eventually settled to the same level (