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Comparative Study
. 2003 Mar;84(3):1563-79.
doi: 10.1016/S0006-3495(03)74967-4.

Heterogeneous presynaptic release probabilities: functional relevance for short-term plasticity

Julia Trommershäuser  1 , Ralf Schneggenburger, Annette Zippelius, Erwin Neher
Affiliations
Comparative Study

Heterogeneous presynaptic release probabilities: functional relevance for short-term plasticity

Julia Trommershäuser et al. Biophys J. 2003 Mar.

Abstract

We discuss a model of presynaptic vesicle dynamics, which allows for heterogeneity in release probability among vesicles. Specifically, we explore the possibility that synaptic activity is carried by two types of vesicles; first, a readily releasable pool and, second, a reluctantly releasable pool. The pools differ regarding their probability of release and time scales on which released vesicles are replaced by new ones. Vesicles of both pools increase their release probability during repetitive stimulation according to the buildup of Ca(2+) concentration in the terminal. These properties are modeled to fit data from the calyx of Held, a giant synapse in the auditory pathway. We demonstrate that this arrangement of two pools of releasable vesicles can account for a variety of experimentally observed patterns of synaptic depression and facilitation at this synapse. We conclude that synaptic transmission cannot be accurately described unless heterogeneity of synaptic release probability is taken into account.

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Figures

FIGURE 1
FIGURE 1
Two-pool model of vesicle recruitment and release. Upon presynaptic stimulation vesicles are released from two different pools that differ regarding their release probability and timescales of recruitment. Reluctantly releasable vesicles (pool 1) are released with a lower release probability (p1) than readily releasable vesicles (pool 2, release probability p2). As indicated by the values assigned to the rate constants of refilling (see Table 1 and Eq. 5), pool 1 recovers faster from depletion than pool 2. The release probabilities of both pools, as well as the rate of recruitment formula image into pool 2, depend on changes in the Ca2+ concentration.
FIGURE 2
FIGURE 2
Effect of elevations in presynaptic Ca2+ concentration on release probability and local Ca2+ concentrations. (A) Dependence of the release probabilities p1 (black lines) and p2 (red lines) on elevations in the global calcium concentration ΔCa2+ as computed from the facilitation model (Eqs. 9 and 10, dashed lines) and the buffered diffusion model (Eqs. 9 and A10, solid lines; see also Appendix A). (B) Dependence of the local calcium concentration [Ca2+]j (j = 1,2) triggering release from pool 1 (black lines) and pool 2 (red lines) on changes in residual calcium ΔCa2+ as computed from Eq. A10 (solid lines). The parameter KD denotes the elevation in [Ca2+]j (j = 1,2) for half-maximal increase in ΔCa2+. For ΔCa2+ < KD, Eq. A10 can be approximated by the linear relation in Eq. 10 (dashed lines). The local calcium concentration [Ca2+]1 (black lines) for a reluctantly releasable vesicle (pool 1) is displaced downward by the constant decrement α (see Eq. 10).
FIGURE 3
FIGURE 3
Comparison of the single-pool model to experimental data. Steady-state EPSC amplitudes (normalized with respect to the first AP in the stimulus train) as a function of frequency. The model is compared to experiments (data taken from von Gersdorff et al., 1997) for two different release probabilities, prest = 0.14 (open squares) and prest = 0.2 (filled triangles). The parameters of the single-pool model (Weis et al., 1999) are constrained by the experimental estimates in Table 1. Lines indicate the predictions of the single-pool model after facilitation of release has been included in the model (prest = 0.14, solid line; prest = 0.2, dashed line).
FIGURE 4
FIGURE 4
Comparison of the two-pool model to experimental data. (A) Steady-state EPSC amplitudes (normalized with respect to the first AP in the stimulus train) as function of frequency (von Gersdorff et al., 1997). The two-pool model (blue solid line) was fitted to the experimental data using p1 (at rest) and γ as fit parameters, rest of parameters constrained by experimental estimates (Table 1). The dot-dashed red line displays predictions of a two-pool model ignoring facilitation of release. The black dashed and black solid line correspond to the fits of the constrained single-pool model from Fig 3 B; depression of EPSC amplitudes during 10 Hz stimulus trains (normalized to the first EPSC; data from Meyer et al., 2001) . The prediction by the four types of models shown in A are displayed. Note that the single-pool models (black lines) tend to underestimate EPSC amplitudes during the steady-state phase of depression.
FIGURE 5
FIGURE 5
Pool dynamics during and after repetitive stimulation. Model predictions of the two-pool model during and after stimulation with 10 Hz (thick black line) and 100 Hz (black line); parameters in Table 1. (A) Occupancy in pool 1. (B) Occupancy in pool 2. The arrow indicates the Ca2+-enhanced recovery at the end of the stimulus train. (C) Facilitation of the release probabilities p1 (open circles) and p2 (solid circles). Circles indicate the release probability at the time of stimulation (larger circles for stimulation with 10 Hz). (D) Elevation in the global calcium concentration [Ca2+]gl during repetitive stimulation as computed by Eq. 13. (E) Recovery after repetitive stimulation with 200 Hz (50 stimuli).
FIGURE 6
FIGURE 6
Steady-state EPSC amplitudes as function of frequency. Predictions of the two-pool model (blue solid line, parameters as in Fig. 4) over a wide range of stimulation frequencies (amplitudes normalized with respect to the first AP in the stimulus train). Predictions of the single-pool model (dashed line) taken from Fig. 3; experimental data from von Gersdorff et al. (1997). The dot-dashed line indicates an ∼1/f-decay.
FIGURE 7
FIGURE 7
Geometric configuration of Ca2+ channels around a release site. A single Ca2+ channel at distance r0 is colocalized with the release site (black circle), which itself is surrounded by a cluster of Ca2+ channels (hatched circles); average area per channel formula image cluster radius r2 (after Fig. 1 A in Neher, 1998a).
FIGURE 8
FIGURE 8
Comparison of the two facilitation models for varying elevations in global and extracellular Ca2+ concentration. The solid line corresponds to the buffered diffusion model (Eqs. 9 and A10); see Table 2 for the values assigned to the model parameters. Circles represent the fit of the calcium-binding-site model (Eq. B11) using formula image and Kd,j (j = 1, 2) as fit parameters (see Table 3); equivalent initial release probabilities (formula image for j = 1,2) assigned for both models. (A) Release probability p2 from pool 2 as function of elevations in global calcium ΔCa2+. (B) Release probability p1.
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References

    1. Abbott, L. F., J. A. Varela, K. Sen, and S. B. Nelson. 1997. Synaptic depression and cortical gain control. Science. 275:220–224. - PubMed
    1. Aharon, S., H. Parnas, and I. Parnas. 1994. The magnitude and significance of Ca2+ domains for release of neurotransmitter. Bull. Math. Biol. 56:1095–1119. - PubMed
    1. Allen, C., and C. F. Stevens. 1994. An evaluation of causes for unreliability of synaptic transmission. Proc. Natl. Acad. Sci. USA. 91:10380–10383. - PMC - PubMed
    1. Bennett, M. R., N. Calckos, and R. H. Scheller. 1992. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 257:255–259. - PubMed
    1. Bertram, R., A. Sherman, and E. F. Stanley. 1996. Single-domain/bound calcium hypothesis of transmitter release and facilitation. J. Neurophysiol. 75:1919–1931. - PubMed

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