Short-Term Synaptic Depression and Recovery at the Mature Mammalian Endbulb of Held Synapse in Mice

Short-term synaptic depression mainly reflects the depletion of the readily releasable pool (RRP) of quanta. Its dynamics, and especially the replenishment rate of the RRP, are still not well characterized in spite of decades of investigation. Main reason is that the vesicular storage and release system is treated as time-independent. If it is time-dependent all parameters thus estimated become problematic. Indeed the reports about how prolonged stimulation affects the dynamics are contradictory. To study this, we used patterned stimulation on the Schaeffer collateral fiber pathway and model-fitting of the excitatory post-synaptic currents (EPSC) recorded from CA1 neurons in rat hippocampal slices. The parameters of a vesicular storage and release model with two pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. This yields the 'basic' parameters (release coupling, replenishment coupling and RRP size) that underlie the 'derived' and commonly used parameters (fractional release and replenishment rate). The fractional release increases when [Ca ?? ] o is raised, whereas the replenishment rate is [Ca ?? ] o independent. Fractional release rises because release coupling increases, and the RRP becomes less able to contain quanta. During prolonged stimulation, the fractional release remains generally unaltered, whereas the replenishment rate decreases down to *10 % of its initial value with a decay time of *15 s, and this decrease in the replenishment rate significantly contributes to synaptic depression. In conclusion, the fractional release is [Ca ?? ] odependent and stimulation-independent, whereas the replenishment rate is [Ca ?? ] o -independent and stimulation-dependent.

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“…This (Dittman and Regehr 1998;Wang and Manis 2008). This discrepancy may be due to the fact that the [Ca ?? ]…”

Section: Discussionmentioning

confidence: 97%

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Bui

Glavinović

2012

Cogn Neurodyn

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“…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). Our data contained few long intervals caused by high spontaneous event rates, but the lack of recovery from depression even after intense stimulation (input rates Ͼ Ͼ300 spikes/s) is inconsistent with large tonic depression, assuming similar presynaptic calcium dynamics in vivo and in vitro.…”

Section: Low Release Probability Of the Endbulb Of Held In Vivomentioning

confidence: 99%

“…During high-frequency stimulation, the rodent endbulb synapse shows synaptic depression in slice recordings (Bellingham and Walmsley, 1999;Oleskevich et al, 2000;Wang and Manis, 2008;Yang and Xu-Friedman, 2008;Cao et al, 2010;Chanda and Xu-Friedman, 2010a,b). In the depressed state, multiple endbulb inputs may be needed to trigger a spike in the SBC (Yang and Xu-Friedman, 2009).…”

Section: Introductionmentioning

confidence: 99%

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

Kuenzel¹,

Borst²,

Heijden³

2011

J. Neurosci.

141

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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.

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“…Recovery from depression had similar biexponential times courses in both avian cochlear nuclei (Brenowitz and Trussell 2001a;MacLeod et al 2007;MacLeod and Horiuchi 2011), suggesting common activity-dependent mechanisms that accelerate recovery rates or the presence of multiple vesicle pools with heterogeneous recovery kinetics. The recovery trajectories in the avian cochlear nuclei thus have similarities to recovery trajectories found in mammalian auditory brain stem and several other areas (Dittman et al 2000;Hallermann et al 2010;Wang and Kaczmarek 1998;Wang and Manis 2008;Wu and Borst 1999;Yang and Xu-Friedman 2008). Rapidly desensitizing glutamate receptors are expressed in both NA and NM (Parks 2000;Raman et al 1994;Sugden et al 2002).…”

mentioning

confidence: 75%

“…In NM the plasticity is dominated by short-term depression (Brenowitz and Trussell 2001a;Zhang and Trussell 1994), while in NA the plasticity is a balanced mixture of facilitation and depression (MacLeod et al 2007). In the mammalian cochlear nucleus, a similar distinction in STP profiles can be observed at nerve terminals onto the bushy cells and those onto stellate cells, which form analogous pathways to NM and NA, respectively (Cao et al 2008;Cao and Oertel 2010;Oleskevich and Walmsley 2002;Wang and Manis 2008;Yang and Xu-Friedman 2008). Differential synaptic dynamics therefore could contribute to the divergence of acoustic timing and intensity information into parallel pathways in the auditory brain stems of birds and mammals.…”

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confidence: 84%

Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus

Ahn

MacLeod

2016

Journal of Neurophysiology

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Ahn J, MacLeod KM. Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus. J Neurophysiol 115: 1679 -1690, 2016. First published December 30, 2015 doi:10.1152/jn.00752.2015.-Short-term synaptic plasticity (STP) acts as a time-and firing rate-dependent filter that mediates the transmission of information across synapses. In the auditory brain stem, the divergent pathways that encode acoustic timing and intensity information express differential STP. To investigate what factors determine the plasticity expressed at different terminals, we tested whether presynaptic release probability differed in the auditory nerve projections to the two divisions of the avian cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Estimates of release probability were made with an openchannel blocker of N-methyl-D-aspartate (NMDA) receptors. Activity-dependent blockade of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) with application of 20 M (ϩ)-MK801 maleate was more rapid in NM than in NA, indicating that release probability was significantly higher at terminals in NM. Paired-pulse ratio (PPR) was tightly correlated with the blockade rate at terminals in NA, suggesting that PPR was a reasonable proxy for relative release probability at these synapses. To test whether release probability was similar across convergent inputs onto NA neurons, PPRs of different nerve inputs onto the same postsynaptic NA target neuron were measured. The PPRs, as well as the plasticity during short trains, were tightly correlated across multiple inputs, further suggesting that release probability is coordinated at auditory nerve terminals in a target-specific manner. This highly specific regulation of STP in the auditory brain stem provides evidence that the synaptic dynamics are tuned to differentially transmit the auditory information in nerve activity into parallel ascending pathways.short-term plasticity; depression; angularis; release probability; magnocellularis

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Short-Term Synaptic Depression and Recovery at the Mature Mammalian Endbulb of Held Synapse in Mice

Cited by 93 publications

References 67 publications

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

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

Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus

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