How Secure Is In Vivo Synaptic Transmission at the Calyx of Held?

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141

Despite the presence of large endbulb inputs, the spherical bushy cells (SBCs) of the rostral anteroventral cochlear nucleus do not function as simple auditory relays. We used the good signal-to-noise ratio of juxtacellular recordings to dissect the intrinsic and network mechanisms controlling the input-output relationship of SBCs in anesthetized gerbils. The SBCs generally operated close to action potential (AP) threshold and showed no evidence for synaptic depression, suggesting that the endbulbs of Held have low release probability in vivo. Analysis of the complex waveforms suggested that in the absence of auditory stimulation, postsynaptic spike depression and stochastic fluctuations in EPSP size were the main factors determining jitter and reliability of the endbulb synapse. During auditory stimulation, progressively larger EPSPs were needed to trigger APs at increasing sound intensities. Simulations suggested hyperpolarizing inhibition could explain the observed decrease in EPSP efficacy. Synaptic inhibition showed a delayed onset and generally had a higher threshold than excitatory inputs, but otherwise inhibition and excitation showed mostly overlapping frequency-response areas. The recruitment of synaptic inhibition caused postsynaptic spikes to be preferentially triggered by well-timed, large EPSPs, resulting in improved phase locking despite more variable EPSP-AP latencies. Our results suggest that the lack of synaptic depression, caused by low release probability, and the apparent absence of sound-evoked synaptic inhibition at low sound intensity maximize sensitivity of SBCs. At higher sound intensities, the recruitment of synaptic inhibition constrains their firing rate and optimizes their temporal precision.

Section: Mechanisms Of Inhibitionsupporting

confidence: 86%

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

Kuenzel¹,

Borst²,

Heijden³

2011

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141

“…Recent in vivo studies in young adult mice (ϳP32) and adult cats reported an activity-dependent decrease of A Post at very short ISIs (Mc Laughlin et al, 2008: AP depression for ISI Ͻ 20 ms; Lorteije et al, 2009: AP depression for ISI Ͻ 10 ms). We found a similar effect, which was strongly pronounced during early postnatal development (consistent with the Fig.…”

Section: Preceding Activity Predicts Variations In Postsynaptic Ap Ammentioning

confidence: 99%

“…The properties of spiking have been shown to depend on previous activity (Fedchyshyn and Wang, 2007;Mc Laughlin et al, 2008;Lorteije et al, 2009;Tolnai et al, 2009). Usually, the last interspike interval (ISI) is used as the independent variable.…”

Section: Failures Of Ap Transmissionmentioning

confidence: 99%

The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo

Sonntag¹,

Englitz²,

Typlt³

et al. 2011

The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigated in vivo over a broad range of ages [postnatal day 8 (P8)-P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12-P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.

“…Because of its ability to fire at extraordinarily high rates (Schneggenburger and Forsythe, 2006), a predominant view is that the mature calyx of Held-MNTB synapse is a fail-safe relay (Mc Laughlin et al, 2008;Englitz et al, 2009). However, some studies show that this synapse fails under predepressed conditions as a result of spontaneous activity (Hermann et al, 2007), when decreases in postsynaptic excitability occur (Lorteije et al, 2009) or during high-frequency electrical or acoustic stimulation (Guinan and Li, 1990;Lorteije and Borst, 2011).…”

Section: Introductionmentioning

confidence: 99%

Morphological and Functional Continuum Underlying Heterogeneity in the Spiking Fidelity at the Calyx of Held SynapseIn Vitro

Grande¹,

Wang²

2011

Reliable neuronal spiking is critical for a myriad of computations performed by neural circuits. This is particularly evident for sound localization cues in the auditory brainstem circuits that detect timing and intensity differences of sounds arriving at two ears. The calyx of Held-principal neuron synapse in the medial nucleus of the trapezoid body (MNTB) in this circuit is traditionally viewed as a reliable relay, which converts contralateral excitatory inputs to inhibitory outputs to ipsilateral superior olive neurons that code interaural timing and intensity differences. However, recent studies demonstrated large variability in the incidence of postsynaptic spike failures at this synapse, challenging the view that this synapse is a fail-safe relay. Using combined imaging and paired recordings in mature (P16 -P19) mouse brainstem slices, we show that spike failure rates of MNTB neurons are strongly correlated with differences in gross morphology of the calyx terminal and quantal properties under standard in vitro-and in vivo-like conditions. MNTB neurons innervated by calyces with simple morphologies (mainly digits) express strong short-term synaptic depression and a high incidence of spike failures after high-frequency stimulation. Conversely, MNTB neurons innervated by structurally complex calyces (digits and numerous bouton-like swellings) exhibit initial facilitation followed by slow depression and very few spike failures. Our results indicate that the calyx of Held-MNTB synapse is likely organized as a structural and functional continuum, in that correlated heterogeneities in calyx morphology and short-term plasticity serve as a filter for regulating the inhibition delivered to superior olive neurons during sound localization.