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Neuromodulatory changes in short-term synaptic dynamics may be mediated by two distinct mechanisms of presynaptic calcium entry

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Abstract

Although synaptic output is known to be modulated by changes in presynaptic calcium channels, additional pathways for calcium entry into the presynaptic terminal, such as non-selective channels, could contribute to modulation of short term synaptic dynamics. We address this issue using computational modeling. The neuropeptide proctolin modulates the inhibitory synapse from the lateral pyloric (LP) to the pyloric dilator (PD) neuron, two slow-wave bursting neurons in the pyloric network of the crab Cancer borealis. Proctolin enhances the strength of this synapse and also changes its dynamics. Whereas in control saline the synapse shows depression independent of the amplitude of the presynaptic LP signal, in proctolin, with high-amplitude presynaptic LP stimulation the synapse remains depressing while low-amplitude stimulation causes facilitation. We use simple calcium-dependent release models to explore two alternative mechanisms underlying these modulatory effects. In the first model, proctolin directly targets calcium channels by changing their activation kinetics which results in gradual accumulation of calcium with low-amplitude presynaptic stimulation, leading to facilitation. The second model uses the fact that proctolin is known to activate a non-specific cation current I MI . In this model, we assume that the MI channels have some permeability to calcium, modeled to be a result of slow conformation change after binding calcium. This generates a gradual increase in calcium influx into the presynaptic terminals through the modulatory channel similar to that described in the first model. Each of these models can explain the modulation of the synapse by proctolin but with different consequences for network activity.

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References

  • Abbott, L. F., Varela, J. A., Sen, K., & Nelson, S. B. (1997). Synaptic depression and cortical gain control. Science, 275(5297), 220–224.

    Article  PubMed  CAS  Google Scholar 

  • Ayali, A., Johnson, B. R., & Harris-Warrick, R. M. (1998). Dopamine modulates graded and spike-evoked synaptic inhibition independently at single synapses in pyloric network of lobster. Journal of Neurophysiology, 79(4), 2063–2069.

    PubMed  CAS  Google Scholar 

  • Babich, O., Matveev, V., Harris, A. L., & Shirokov, R. (2007). Ca2+-dependent inactivation of CaV1.2 channels prevents Gd3+ block: does Ca2+ block the pore of inactivated channels? Journal of General Physiology, 129(6), 477–483.

    Article  PubMed  CAS  Google Scholar 

  • Bardoni, R., Torsney, C., Tong, C. K., Prandini, M., & MacDermott, A. B. (2004). Presynaptic NMDA receptors modulate glutamate release from primary sensory neurons in rat spinal cord dorsal horn. Journal of Neuroscience, 24(11), 2774–2781.

    Article  PubMed  CAS  Google Scholar 

  • Barriere, G., Tartas, M., Cazalets, J. R., & Bertrand, S. S. (2008). Interplay between neuromodulator-induced switching of short-term plasticity at sensorimotor synapses in the neonatal rat spinal cord. The Journal of Physiology, 586(7), 1903–1920.

    Article  PubMed  CAS  Google Scholar 

  • Berretta, N., & Jones, R. S. (1996). Tonic facilitation of glutamate release by presynaptic N-methyl-D-aspartate autoreceptors in the entorhinal cortex. Neuroscience, 75(2), 339–344.

    Article  PubMed  CAS  Google Scholar 

  • Bertram, R., Sherman, A., & Stanley, E. F. (1996). Single-domain/bound calcium hypothesis of transmitter release and facilitation. Journal of Neurophysiology, 75(5), 1919–1931.

    PubMed  CAS  Google Scholar 

  • Bertram, R., Swanson, J., Yousef, M., Feng, Z. P., & Zamponi, G. W. (2003). A minimal model for G protein-mediated synaptic facilitation and depression. Journal of Neurophysiology, 90(3), 1643–1653.

    Article  PubMed  CAS  Google Scholar 

  • Bieda, M. C., & Copenhagen, D. R. (2004). N-type and L-type calcium channels mediate glycinergic synaptic inputs to retinal ganglion cells of tiger salamanders. Visual Neuroscience, 21(4), 545–550.

    Article  PubMed  Google Scholar 

  • Borst, J. G., & Sakmann, B. (1998). Facilitation of presynaptic calcium currents in the rat brainstem. The Journal of Physiology, 513(Pt 1), 149–155.

    Article  PubMed  CAS  Google Scholar 

  • Buchholtz, F., Golowasch, J., Epstein, I. R., & Marder, E. (1992). Mathematical model of an identified stomatogastric ganglion neuron. Journal of Neurophysiology, 67(2), 332–340.

    PubMed  CAS  Google Scholar 

  • Chance, F. S., Nelson, S. B., & Abbott, L. F. (1998). Synaptic depression and the temporal response characteristics of V1 cells. Journal of Neuroscience, 18(12), 4785–4799.

    PubMed  CAS  Google Scholar 

  • Cuttle, M. F., Tsujimoto, T., Forsythe, I. D., & Takahashi, T. (1998). Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem. The Journal of Physiology, 512(Pt 3), 723–729.

    Article  PubMed  CAS  Google Scholar 

  • Dittman, J. S., Kreitzer, A. C., & Regehr, W. G. (2000). Interplay between facilitation, depression, and residual calcium at three presynaptic terminals. Journal of Neuroscience, 20(4), 1374–1385.

    PubMed  CAS  Google Scholar 

  • Fossier, P., Tauc, L., & Baux, G. (1999). Calcium transients and neurotransmitter release at an identified synapse. Trends in Neurosciences, 22(4), 161–166.

    Article  PubMed  CAS  Google Scholar 

  • Galarreta, M., & Hestrin, S. (1998). Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex. Nature Neuroscience, 1(7), 587–594.

    Article  PubMed  CAS  Google Scholar 

  • Golowasch, J., & Marder, E. (1992). Proctolin activates an inward current whose voltage dependence is modified by extracellular Ca2+. Journal of Neuroscience, 12(3), 810–817.

    PubMed  CAS  Google Scholar 

  • Gray, M. L., & Golowasch, J. (2011) Intracellular signaling of peptidergic neuromodulatory input to the pyloric network in the stomatogastric ganglion of Cancer borealis. In Soc Neurosci Abst, 2011 (Vol. 37, Vol. 707.04)

  • Gundlfinger, A., Leibold, C., Gebert, K., Moisel, M., Schmitz, D., & Kempter, R. (2007). Differential modulation of short-term synaptic dynamics by long-term potentiation at mouse hippocampal mossy fibre synapses. The Journal of Physiology, 585(Pt 3), 853–865.

    Article  PubMed  CAS  Google Scholar 

  • Hermann, J., Grothe, B., & Klug, A. (2009). Modeling short-term synaptic plasticity at the calyx of held using in vivo-like stimulation patterns. Journal of Neurophysiology, 101(1), 20–30.

    Article  PubMed  Google Scholar 

  • Hige, T., Fujiyoshi, Y., & Takahashi, T. (2006). Neurosteroid pregnenolone sulfate enhances glutamatergic synaptic transmission by facilitating presynaptic calcium currents at the calyx of Held of immature rats. European Journal of Neuroscience, 24(7), 1955–1966.

    Article  PubMed  Google Scholar 

  • Inchauspe, C. G., Martini, F. J., Forsythe, I. D., & Uchitel, O. D. (2004). Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of held presynaptic terminal. Journal of Neuroscience, 24(46), 10379–10383.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa, T., Kaneko, M., Shin, H. S., & Takahashi, T. (2005). Presynaptic N-type and P/Q-type Ca2+ channels mediating synaptic transmission at the calyx of Held of mice. The Journal of Physiology, 568(Pt 1), 199–209.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, B. R., Brown, J. M., Kvarta, M. D., Lu, J. Y., Schneider, L. R., Nadim, F., et al. (2011). Differential modulation of synaptic strength and timing regulate synaptic efficacy in a motor network. Journal of Neurophysiology, 105(1), 293–304.

    Article  PubMed  Google Scholar 

  • Johnson, B. R., Kloppenburg, P., & Harris-Warrick, R. M. (2003). Dopamine modulation of calcium currents in pyloric neurons of the lobster stomatogastric ganglion. Journal of Neurophysiology, 90(2), 631–643.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, B. R., Schneider, L. R., Nadim, F., & Harris-Warrick, R. M. (2005). Dopamine modulation of phasing of activity in a rhythmic motor network: contribution of synaptic and intrinsic modulatory actions. Journal of Neurophysiology, 94(5), 3101–3111.

    Article  PubMed  CAS  Google Scholar 

  • Kreitzer, A. C., & Regehr, W. G. (2000). Modulation of transmission during trains at a cerebellar synapse. Journal of Neuroscience, 20(4), 1348–1357.

    PubMed  CAS  Google Scholar 

  • Lagarias, J. C., Reeds, J. A., Wright, M. H., & Wright, P. E. (1998). Convergence properties of the Nelder-Mead simplex method in low dimensions. SIAM Journal on Optimization, 9(1), 112–147.

    Article  Google Scholar 

  • MacLeod, K. M., Horiuchi, T. K., & Carr, C. E. (2007). A role for short-term synaptic facilitation and depression in the processing of intensity information in the auditory brain stem. Journal of Neurophysiology, 97(4), 2863–2874.

    Article  PubMed  CAS  Google Scholar 

  • Mamiya, A., Manor, Y., & Nadim, F. (2003). Short-term dynamics of a mixed chemical and electrical synapse in a rhythmic network. Journal of Neuroscience, 23(29), 9557–9564.

    PubMed  CAS  Google Scholar 

  • Mamiya, A., & Nadim, F. (2005). Target-specific short-term dynamics are important for the function of synapses in an oscillatory neural network. Journal of Neurophysiology, 94(4), 2590–2602.

    Article  PubMed  Google Scholar 

  • Manor, Y., Bose, A., Booth, V., & Nadim, F. (2003). Contribution of synaptic depression to phase maintenance in a model rhythmic network. Journal of Neurophysiology, 90(5), 3513–3528.

    Article  PubMed  Google Scholar 

  • Manor, Y., Nadim, F., Abbott, L. F., & Marder, E. (1997). Temporal dynamics of graded synaptic transmission in the lobster stomatogastric ganglion. Journal of Neuroscience, 17(14), 5610–5621.

    PubMed  CAS  Google Scholar 

  • Marder, E., & Bucher, D. (2007). Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs. Annual Review of Physiology, 69, 291–316.

    Article  PubMed  CAS  Google Scholar 

  • Markram, H., & Tsodyks, M. (1996). Redistribution of synaptic efficacy between neocortical pyramidal neurons. Nature, 382(6594), 807–810.

    Article  PubMed  CAS  Google Scholar 

  • Matveev, V., Bertram, R., & Sherman, A. (2006). Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic facilitation. Journal of Neurophysiology, 96, 3389–3397.

    Article  PubMed  Google Scholar 

  • Nadim, F., Booth, V., Bose, A., & Manor, Y. (2003). Short-term synaptic dynamics promote phase maintenance in multi-phasic rhythms. Neurocomputing, 52–4, 79–87.

    Article  Google Scholar 

  • Olcese, R. (2007). And yet it moves: conformational States of the Ca2+ channel pore. Journal of General Physiology, 129(6), 457–459.

    Article  PubMed  CAS  Google Scholar 

  • Pan, B., & Zucker, R. S. (2009). A general model of synaptic transmission and short-term plasticity. Neuron, 62(4), 539–554.

    Article  PubMed  CAS  Google Scholar 

  • Reyes, A., Lujan, R., Rozov, A., Burnashev, N., Somogyi, P., & Sakmann, B. (1998). Target-cell-specific facilitation and depression in neocortical circuits. Nature Neuroscience, 1(4), 279–285.

    Article  PubMed  CAS  Google Scholar 

  • Rose, G., & Fortune, E. (1999). Frequency-dependent PSP depression contributes to low-pass temporal filtering in Eigenmannia. Journal of Neuroscience, 19(17), 7629–7639.

    PubMed  CAS  Google Scholar 

  • Schneggenburger, R., & Neher, E. (2005). Presynaptic calcium and control of vesicle fusion. Current Opinion in Neurobiology, 15(3), 266–274.

    Article  PubMed  CAS  Google Scholar 

  • Stout, A. K., Li-Smerin, Y., Johnson, J. W., & Reynolds, I. J. (1996). Mechanisms of glutamate-stimulated Mg2+ influx and subsequent Mg2+ efflux in rat forebrain neurones in culture. The Journal of Physiology, 492(Pt 3), 641–657.

    PubMed  CAS  Google Scholar 

  • Swensen, A. M., & Marder, E. (2000). Multiple peptides converge to activate the same voltage-dependent current in a central pattern-generating circuit. Journal of Neuroscience, 20(18), 6752–6759.

    PubMed  CAS  Google Scholar 

  • Swensen, A. M., & Marder, E. (2001). Modulators with convergent cellular actions elicit distinct circuit outputs. Journal of Neuroscience, 21(11), 4050–4058.

    PubMed  CAS  Google Scholar 

  • Thies, R. E. (1965). Neuromuscular depression and the apparent depletion of transmitter in mammalian muscle. Journal of Neurophysiology, 28, 428–442.

    PubMed  CAS  Google Scholar 

  • Thirumalai, V., Prinz, A. A., Johnson, C. D., & Marder, E. (2006). Red pigment concentrating hormone strongly enhances the strength of the feedback to the pyloric rhythm oscillator but has little effect on pyloric rhythm period. Journal of Neurophysiology, 95(3), 1762–1770.

    Article  PubMed  CAS  Google Scholar 

  • Tsodyks, M., Pawelzik, K., & Markram, H. (1998). Neural networks with dynamic synapses. Neural Computation, 10(4), 821–835.

    Article  PubMed  CAS  Google Scholar 

  • Tsodyks, M. V., & Markram, H. (1997). The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proceedings of the National Academy of Sciences of the United States of America, 94(2), 719–723.

    Article  PubMed  CAS  Google Scholar 

  • Tsujimoto, T., Jeromin, A., Saitoh, N., Roder, J. C., & Takahashi, T. (2002). Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium currents at presynaptic nerve terminals. Science, 295(5563), 2276–2279.

    Article  PubMed  CAS  Google Scholar 

  • Verhoog, M. B., & Mansvelder, H. D. (2011). Presynaptic ionotropic receptors controlling and modulating the rules for spike timing-dependent plasticity. Neural Plasticity, 2011, 870763.

    Article  PubMed  Google Scholar 

  • von Gersdorff, H., Schneggenburger, R., Weis, S., & Neher, E. (1997). Presynaptic depression at a calyx synapse: the small contribution of metabotropic glutamate receptors. Journal of Neuroscience, 17(21), 8137–8146.

    Google Scholar 

  • Wang, S. J., Wang, K. Y., Wang, W. C., & Sihra, T. S. (2006). Unexpected inhibitory regulation of glutamate release from rat cerebrocortical nerve terminals by presynaptic 5-hydroxytryptamine-2A receptors. Journal of Neuroscience Research, 84(7), 1528–1542.

    Article  PubMed  CAS  Google Scholar 

  • Wu, L. G., & Betz, W. J. (1998). Kinetics of synaptic depression and vesicle recycling after tetanic stimulation of frog motor nerve terminals. Biophysical Journal, 74(6), 3003–3009.

    Article  PubMed  CAS  Google Scholar 

  • Wu, L. G., & Saggau, P. (1997). Presynaptic inhibition of elicited neurotransmitter release. Trends in Neurosciences, 20(5), 204–212.

    Article  PubMed  CAS  Google Scholar 

  • Xu, J., He, L., & Wu, L. G. (2007). Role of Ca(2+) channels in short-term synaptic plasticity. Current Opinion in Neurobiology, 17(3), 352–359.

    Article  PubMed  CAS  Google Scholar 

  • Xu, J., & Wu, L. G. (2005). The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse. Neuron, 46(4), 633–645.

    Article  PubMed  CAS  Google Scholar 

  • Yue, D. T., Backx, P. H., & Imredy, J. P. (1990). Calcium-sensitive inactivation in the gating of single calcium channels. Science, 250(4988), 1735–1738.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, S., Sheibanie, A. F., Oh, M., Rabbah, P., & Nadim, F. (2011). Peptide neuromodulation of synaptic dynamics in an oscillatory network. Journal of Neuroscience, 31(39), 13991–14004.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, L., Zhao, S., & Nadim, F. (2007). Neuromodulation of short-term synaptic dynamics examined in a mechanistic model based on kinetics of calcium currents. Neurocomputing, 70(10–12), 2050–2054.

    Article  PubMed  Google Scholar 

  • Zucker, R. S., & Regehr, W. G. (2002). Short-term synaptic plasticity. Annual Review of Physiology, 64, 355–405.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Science Foundation grant DMS-0817703 (VM) and the National Institute of Mental Health grant MH060605 (FN).

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Correspondence to Farzan Nadim.

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Oh, M., Zhao, S., Matveev, V. et al. Neuromodulatory changes in short-term synaptic dynamics may be mediated by two distinct mechanisms of presynaptic calcium entry. J Comput Neurosci 33, 573–585 (2012). https://doi.org/10.1007/s10827-012-0402-z

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