Neurons are often considered to be the computational engines of the brain, with synapses acting solely as conveyers of information. But the diverse types of synaptic plasticity and the range of timescales over which they operate suggest that synapses have a more active role in information processing. Long-term changes in the transmission properties of synapses provide a physiological substrate for learning and memory, whereas short-term changes support a variety of computations. By expressing several forms of synaptic plasticity, a single neuron can convey an array of different signals to the neural circuit in which it operates.
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Brown, R. E. & Milner, P. M. The legacy of Donald O. Hebb: more than the Hebb synapse. Nature Rev. Neurosci. 4, 1013–1019 (2003).
Lynch, M. A. Long-term potentiation and memory. Physiol. Rev. 84, 87–136 (2004).
Morris, R. G. Long-term potentiation and memory. Phil. Trans. R. Soc. Lond. B 358, 643–647 (2003).
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998).
Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004).
Burrone, J. & Murthy, V. N. Synaptic gain control and homeostasis. Curr. Opin. Neurobiol. 13, 560–567 (2003).
Zucker, R. S. & Regehr, W. G. Short-term synaptic plasticity. Annu. Rev. Physiol. 64, 355–405 (2002).
Eccles, J. C. The Physiology of Synapses (Springer-Verlag, New York, 1964).
Katz, B. Nerve, Muscle and Synapse (McGraw Hill, New York, 1966).
Kandel, E. K., Schwartz, J. H. & Jessel, T. M. Principles of Neural Science, 1414 (McGraw-Hill/Appleton & Lange, 2000).
Trommershauser, J., Schneggenburger, R., Zippelius, A. & Neher, E. Heterogeneous presynaptic release probabilities: functional relevance for short-term plasticity. Biophys. J. 84, 1563–1579 (2003).
Reyes, A. et al. Target-cell-specific facilitation and depression in neocortical circuits. Nature Neurosci. 1, 279–285 (1998).
Markram, H., Wang, Y. & Tsodyks, M. Differential signaling via the same axon of neocortical pyramidal neurons. Proc. Natl Acad. Sci. USA 95, 5323–5328 (1998).
Auger, C. & Marty, A. Quantal currents at single-site central synapses. J. Physiol. 526(I), 3–11 (2000).
Magleby, K. L. in Synaptic Function (eds Edelman, G. M., Gall, W. E. & Cowan, W. M.) 21–56 (Wiley, New York, 1987).
Freund, T. F., Katona, I. & Piomelli, D. Role of endogenous cannabinoids in synaptic signaling. Physiol. Rev. 83, 1017–1066 (2003).
Fitzsimonds, R. M. & Poo, M. M. Retrograde signaling in the development and modification of synapses. Physiol. Rev. 78, 143–170 (1998).
Trussell, L. O. & Fischbach, G. D. Glutamate receptor desensitization and its role in synaptic transmission. Neuron 3, 209–218 (1989).
Blitz, D. M. & Regehr, W. G. Retinogeniculate synaptic properties controlling spike number and timing in relay neurons. J. Neurophysiol. 90, 2438–2450 (2003).
Chen, C., Blitz, D. M. & Regehr, W. G. Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. Neuron 33, 779–788 (2002).
Jones, M. V. & Westbrook, G. L. The impact of receptor desensitization on fast synaptic transmission. Trends Neurosci. 19, 96–101 (1996).
Xu-Friedman, M. A. & Regehr, W. G. Ultrastructural contributions to desensitization at cerebellar mossy fiber to granule cell synapses. J. Neurosci. 23, 2182–2192 (2003).
Conn, P. J. Physiological roles and therapeutic potential of metabotropic glutamate receptors. Ann. NY Acad. Sci. 1003, 12–21 (2003).
Johnston, D. et al. Active dendrites, potassium channels and synaptic plasticity. Phil. Trans. R. Soc. Lond. B 358, 667–674 (2003).
Hausser, M., Spruston, N. & Stuart, G. J. Diversity and dynamics of dendritic signaling. Science 290, 739–744 (2000).
Craig, A. M. & Boudin, H. Molecular heterogeneity of central synapses: afferent and target regulation. Nature Neurosci. 4, 569–578 (2001).
Thomson, A. M., Bannister, A. P., Mercer, A. & Morris, O. T. Target and temporal pattern selection at neocortical synapses. Phil. Trans. R. Soc. Lond. B 357, 1781–1791 (2002).
Llano, I., Leresche, N. & Marty, A. Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6, 565–574 (1991).
Pitler, T. A. & Alger, B. E. Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells. J. Neurosci. 12, 4122–4132 (1992).
Kreitzer, A. C. & Regehr, W. G. Retrograde signaling by endocannabinoids. Curr. Opin. Neurobiol. 12, 324–330 (2002).
Wilson, R. I. & Nicoll, R. A. Endocannabinoid signaling in the brain. Science 296, 678–682 (2002).
Chavkin, C. Dynorphins are endogenous opioid peptides released from granule cells to act neurohumorly and inhibit excitatory neurotransmission in the hippocampus. Prog. Brain Res. 125, 363–367 (2000).
Kombian, S. B., Mouginot, D. & Pittman, Q. J. Dendritically released peptides act as retrograde modulators of afferent excitation in the supraoptic nucleus in vitro. Neuron 19, 903–912 (1997).
Tao, H. W. & Poo, M. Retrograde signaling at central synapses. Proc. Natl Acad. Sci. USA 98, 11009–11015 (2001).
Wilson, R. I. & Nicoll, R. A. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410, 588–592 (2001).
Kreitzer, A. C. & Regehr, W. G. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. Neuron 29, 717–727 (2001).
Ohno-Shosaku, T., Maejima, T. & Kano, M. Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron 29, 729–738 (2001).
Brenowitz, S. D. & Regehr, W. G. Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells. J. Neurosci. 23, 6373–6384 (2003).
Brown, S. P., Brenowitz, S. D. & Regehr, W. G. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nature Neurosci. 6, 1048–1057 (2003).
Gerdeman, G. L., Ronesi, J. & Lovinger, D. M. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nature Neurosci. 5, 446–451 (2002).
Chevaleyre, V. & Castillo, P. E. Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. Neuron 38, 461–472 (2003).
Sjostrom, P. J., Turrigiano, G. G. & Nelson, S. B. Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Neuron 39, 641–654 (2003).
von der Malsburg, C. & Schneider, W. A neural cocktail-party processor. Biol. Cybern. 54, 29–40 (1986).
Sandberg, A., Tegner, J. & Lansner, A. A working memory model based on fast Hebbian learning. Network 14, 789–802 (2003).
Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000).
Liaw, J. S. & Berger, T. W. Dynamic synapse: a new concept of neural representation and computation. Hippocampus 6, 591–600 (1996).
Okatan, M. & Grossberg, S. Frequency-dependent synaptic potentiation, depression and spike timing induced by Hebbian pairing in cortical pyramidal neurons. Neural Netw. 13, 699–708 (2000).
Dittman, J. S., Kreitzer, A. C. & Regehr, W. G. Interplay between facilitation, depression, and residual calcium at three presynaptic terminals. J. Neurosci. 20, 1374–1385 (2000).
Fuhrmann, G., Segev, I., Markram, H. & Tsodyks, M. Coding of temporal information by activity-dependent synapses. J. Neurophysiol. 87, 140–148 (2002).
Silberberg, G., Wu, C. & Markram, H. Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit. J. Physiol. 556, 19–27 (2004).
Markram, H., Gupta, A., Uziel, A., Wang, Y. & Tsodyks, M. Information processing with frequency-dependent synaptic connections. Neurobiol. Learn. Mem. 70, 101–112 (1998).
Abbott, L. F., Varela, J. A., Sen, K. & Nelson, S. B. Synaptic depression and cortical gain control. Science 275, 220–224 (1997).
Hopfield, J. J. & Brody, C. D. Learning rules and network repair in spike-timing-based computation networks. Proc. Natl Acad. Sci. USA 101, 337–342 (2004).
Markram, H., Pikus, D., Gupta, A. & Tsodyks, M. Potential for multiple mechanisms, phenomena and algorithms for synaptic plasticity at single synapses. Neuropharmacology 37, 489–500 (1998).
Melamed, O., Gerstner, W., Maass, W., Tsodyks, M. & Markram, H. Coding and learning of behavioral sequences. Trends Neurosci. 27, 11-4; discussion 14-5 (2004).
Maass, W. & Markram, H. Synapses as dynamic memory buffers. Neural Netw. 15, 155–161 (2002).
Fortune, E. S. & Rose, G. J. Roles for short-term synaptic plasticity in behavior. J. Physiol. Paris 96, 539–545 (2002).
O'Donovan, M. J. & Rinzel, J. Synaptic depression: a dynamic regulator of synaptic communication with varied functional roles. Trends Neurosci. 20, 431–433 (1997).
Goldman, M. S., Maldonado, P. & Abbott, L. F. Redundancy reduction and sustained firing with stochastic depressing synapses. J. Neurosci. 22, 584–591 (2002).
Lisman, J. E. Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci. 20, 38–43 (1997).
Thomson, A. M. Presynaptic frequency- and pattern-dependent filtering. J. Comput. Neurosci. 15, 159–202 (2003).
Tsodyks, M. V. & Markram, H. The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc. Natl Acad. Sci. USA 94, 719–723 (1997).
Brenowitz, S., David, J. & Trussell, L. Enhancement of synaptic efficacy by presynaptic GABA(B) receptors. Neuron 20, 135–141 (1998).
Trussell, L. O., Zhang, S. & Raman, I. M. Desensitization of AMPA receptors upon multiquantal neurotransmitter release. Neuron 10, 1185–1196 (1993).
Brenowitz, S. & Trussell, L. O. Minimizing synaptic depression by control of release probability. J. Neurosci. 21, 1857–1867 (2001).
Chance, F. S., Nelson, S. B. & Abbott, L. F. Synaptic depression and the temporal response characteristics of V1 cells. J. Neurosci. 18, 4785–4799 (1998).
Carandini, M., Heeger, D. J. & Senn, W. A synaptic explanation of suppression in visual cortex. J. Neurosci. 22, 10053–10065 (2002).
Freeman, T. C., Durand, S., Kiper, D. C. & Carandini, M. Suppression without inhibition in visual cortex. Neuron 35, 759–771 (2002).
Maass, W. & Zador, A. M. Dynamic stochastic synapses as computational units. Neural Comput. 11, 903–917 (1999).
Zador, A. M. & Dobrunz, L. E. Dynamic synapses in the cortex. Neuron 19, 1–4 (1997).
Kuba, H., Koyano, K. & Ohmori, H. Synaptic depression improves coincidence detection in the nucleus laminaris in brainstem slices of the chick embryo. Eur. J. Neurosci. 15, 984–990 (2002).
Cook, D. L., Schwindt, P. C., Grande, L. A. & Spain, W. J. Synaptic depression in the localization of sound. Nature 421, 66–70 (2003).
Konishi, M. Coding of auditory space. Annu. Rev. Neurosci. 26, 31–55 (2003).
Grossberg, S. in Brain and Information: Event Related Potentials (eds Karrer, R., Cohen, J. & Tueting, P.) 58–142 (New York Academy of Science, New York, 1994).
Chung, S., Li, X. & Nelson, S. B. Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo. Neuron 34, 437–446 (2002).
The authors declare no competing financial interests.
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Abbott, L., Regehr, W. Synaptic computation. Nature 431, 796–803 (2004). https://doi.org/10.1038/nature03010
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