Activity‐dependent changes in temporal components of neurotransmission at the juvenile mouse calyx of Held synapse

The medial nucleus of the trapezoid body (MNTB) receives excitatory input from giant presynaptic terminals, the calyces of Held. The MNTB functions as a sign inverter giving inhibitory input to the lateral and medial superior olive, where its input is important in the generation of binaural sensitivity to cues for sound localization. Extracellular recordings from MNTB neurons show complex spikes consisting of a prepotential, thought to reflect synaptic activation, followed by a postsynaptic action potential. This makes the synapse ideal to study synaptic transmission in vivo because presynaptic and postsynaptic activity can be monitored with a single electrode. Recent in vivo and in vitro studies have observed isolated prepotentials in the MNTB suggesting that, under certain stimulus conditions, synaptic transmission fails. We investigated synaptic transmission at the calyx of Held in the MNTB of the adult cat and concluded that synaptic transmission was completely secure in terms of rate of transmitted spikes. However, synaptic transmission was found to be less secure in terms of timing. With increasing spike rate, the synaptic delay showed an increase of up to 100 s, as well as a decrease in amplitude of the action potential. This variability in delay is of a surprisingly high magnitude given the hypothesized role of these binaural circuits in sound localization and given the fact that this is one of the largest synapses in the mammalian brain.

Section: Intraspike Intervals and Peak Amplitudementioning

confidence: 67%

How Secure IsIn VivoSynaptic Transmission at the Calyx of Held?

Laughlin

Heijden²,

Joris³

2008

“…stimulation in vivo, significant activity-dependent changes in the transmission delay also occur at the mature calyx of Held (Fedchyshyn and Wang, 2007;Mc Laughlin et al, 2008;Tolnai et al, 2009). Thus, during high-frequency firing (Ͼ200 Hz), the retention of temporal precision of signal transmission might be limited even at the mature calyx of Held.…”

Section: Development Of Activity-dependent Plasticitymentioning

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.

“…6). Interestingly, a recent study found a frequency-dependent slowing of the EPSC rise time in fiber stimulation experiments (Fedchyshyn and Wang, 2007) that might be caused by the same mechanism. We interpret the slowing of the fast release component seen in Ca 2ϩ uncaging experiments as evidence for a preexisting heterogeneity of release kinetics among FRP vesicles.…”

Section: Mechanism Of Facilitation In the Depressed State Of The Synapsementioning

confidence: 99%

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

Müller

Goutman²,

Kochubey³

et al. 2010

The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Held synapses. Stimulation at a "low" frequency of 10 or 20 Hz, which is in the range of the spontaneous activity of these auditory neurons in vivo, induced synaptic depression. Surprisingly, an instantaneous increase of the stimulation frequency to 100 or 200 Hz following the low-frequency train uncovered a robust facilitation of EPSCs relative to the predepressed amplitude level. This facilitation decayed rapidly (ϳ30 ms) and depended on presynaptic residual Ca 2ϩ , but it was not caused by Ca 2ϩ current facilitation. To probe the release probability of the remaining readily releasable vesicles following the low-frequency train we made presynaptic Ca 2ϩ uncaging experiments in the predepressed state of the synapse. We found that low-frequency stimulation depletes the fast-releasable vesicle pool (FRP) down to ϳ40% of control and that the remaining FRP vesicles are released with ϳ2-fold slower release kinetics, indicating a hitherto unknown intrinsic heterogeneity among FRP vesicles. Thus, vesicles with an intrinsically lower release probability predominate after low frequency stimulation and undergo facilitation during the onset of subsequent high-frequency trains. Facilitation in the predepressed state of the synapse might help to stabilize the amount of transmitter release at the onset of high-frequency firing at these auditory synapses.