Synaptic Transmission at the Calyx of Held Under In Vivo–Like Activity Levels

Abstract

One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound-evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (< or =800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain stem slices. Here we first determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian gerbils and then reintroduce this random firing to in vitro gerbil brain stem synapses at near-physiological temperature. After conditioning synapses with afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60 Hz, we observed a number of differences in the properties of synaptic transmission between conditioned and unconditioned synapses. Foremost, we observed reduced steady-state EPSC amplitudes that depressed even further during an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus simulates in vitro what probably occurs at the in vivo MNTB after a short sound stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of action potential failures at the postsynaptic cell during high-frequency-stimulation trains, although the initial onset of evoked activity was still transmitted with higher fidelity. We thus propose that some in vivo auditory synapses are in a tonic state of reduced EPSC amplitudes as a consequence of high spontaneous spiking and this in vivo-like conditioning has important consequences for the encoding of signals throughout the auditory pathway.

Similar Intracellular Ca2+Requirements for Inactivation and Facilitation of Voltage-Gated Ca2+Channels in a Glutamatergic Mammalian Nerve Terminal

“…Within the MNTB of adult rats, spontaneous discharge rates vary between zero and 133 Hz (mean 29 Hz, Tolnai et al, 2008). Similar values have been reported for gerbils (mean 25 Hz, Hermann et al, 2007). Even higher spontaneous rates were measured in adult mice (mean 71 Hz, range 0.4 -174 Hz, Lorteije et al, 2009).…”

Factors Controlling the Input–Output Relationship of Spherical Bushy Cells in the Gerbil Cochlear Nucleus

“…We address tonic depression as a final candidate. Most cells are silent in slices, but in vivo their spontaneous activity may induce tonic short-term synaptic depression (Boudreau and Ferster, 2005;Reig et al, 2006;Hermann et al, 2007;Wang et al, 2010). In slices, a fast recovery phase has been observed, which depends on calcium buildup within the endbulb (Wang and Manis, 2008;Yang and Xu-Friedman, 2008).…”

Interaction between Facilitation and Depression at a Large CNS Synapse Reveals Mechanisms of Short-Term Plasticity

“…Recent work has shown that synaptic depression observed after long stimulation pauses in slice preparations might be less relevant in vivo (Hermann et al, 2007;Lorteije et al, 2009), mainly because of the high rates of spontaneous firing. Our work suggests that sudden increases in the rate of afferent fiber firing during sound-evoked activity might induce facilitation in the predepressed state of the synapse similar to the facilitation observed here in slice recordings.…”

“…However, in vivo, neurons in the auditory brainstem fire spontaneously at a mean frequency of ϳ10 -30 Hz even in the absence of sound, and sound stimulation can transiently increase AP frequency to several hundred hertz (Sommer et al, 1993;Kopp-Scheinpflug et al, 2003;Hermann et al, 2007;Sonntag et al, 2009). In the present study, we used the most basic stimulation protocol designed to mimic the effect of spontaneous AP firing on short-term plasticity: a brief low-frequency train (10 or 20 Hz) to predepress synaptic transmission, followed immediately by a high-frequency train (see also Hermann et al, 2007). When applying this protocol to calyx of Held synapses in slices of young rats, we found that high-frequency trains (100 -200 Hz) caused robust facilitation of transmitter release relative to the predepressed level.…”