Abstract
Long-term potentiation (LTP), the long-lasting increase in synaptic transmission, has been proposed to be a cellular mechanism essential for learning and memory, neuronal development, andcircuit reorganization. In the original theoretical1 and experimental2 work it was assumed that only synapses that had experienced concurrent pre- and postsynaptic activity are subject to synaptic modification. It has since been shown, however, that LTP is also expressed in synapses on neighbouring neurons that have not undergone the induction procedure3,4,5. Yet, it is still believed that this spread of LTP is limited to adjacent postsynaptic cells, and does not occur for synapses on neighbouring input fibres2,6,7. However, for technical reasons, tests for ‘input specificity’ were always done for synapses relatively far apart. Here we have used a new local superfusion technique, which allowed us to assess the synaptic specificity of LTP with a spatial resolution of ∼30μm. Our results indicate that there is no input specificity at a distance of less than 70μm. Synapses in close proximity to a site of potentiation are also potentiated regardless of their own history of activation, whereas synapses far away show no potentiation.
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References
Hebb, D. O. The Organization of Behavior. A Neuropsychological Theory (Wiley, New York, (1949)).
Gustafsson, B., Wigström, H., Abraham, W. C. & Huang, Y.-Y. Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials. J. Neurosci. 7, 774–780 (1987).
Bonhoeffer, T., Staiger, V. & Aertsen, A. Synaptic plasticity in rat hippocampal slice cultures: local “Hebbian” conjunction of pre- and postsynaptic stimulation leads to distributed synaptic enhancement. Proc. Nat Acad. Sci. USA 86, 8113–8117 (1989).
Kossel, A., Bonhoeffer, T. & Bolz, J. Non-Hebbian synapses in rat visual cortex. NeuroReport 1, 115–118 (1990).
Schuman, E. M. & Madison, D. V. Locally distributed synaptic potentiation in the hippocampus. Science 263, 532–536 (1994).
Muller, D., Hefft, S. & Figurov, A. Heterosynaptic interactions between LTP and LTD in CA1 hippocampal slices. Neuron 14, 599–605 (1996).
Scanziani, M., Malenka, R. C. & Nicoll, R. A. Role of intercellular interactions in heterosynaptic long-term depression. Nature 380, 446–450 (1996).
Gähwiler, B. H. Morphological differentiation of nerve cells in thin organotypic cultures derived from rat hippocampus and cerebellum. Proc. R. .Soc. Lond. B 211, 287–290 (1981).
Veselovsky, N. S., Engert, F. & Lux, H. D. Fast local superfusion technique. Pflügers Arch. 432, 351–354 (1996).
Hessler, N. A., Shirke, A. M. & Malinow, R. The probability of transmitter release at a mammalian central synapse. Nature 366, 569–572 (1993).
Lipski, J. Antidromic activation of neurones as an analytical tool in the study of the central nervous system. J. Neurosci. Methods 4, 1–32 (1981).
Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71–75 (1996).
Otani, S., Connor, J. A. & Levy, W. B. Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus. Learn. Mem. 2, 101–106 (1995).
Williams, J. H., Errington, M. L., Lynch, M. A. & Bliss, T. V. P. Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature 341, 739–742 (1989).
Schuman, E. M. & Madison, D. V. Arequirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254, 1503–1506 (1991).
Arancio, O. et al. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiaiton in cultured hippocampal neurons. Cells 87, 1025–1035 (1996).
Malinow, R. & Tsien, R. W. Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices. Nature 346, 177–180 (1990).
Larkman, A. U., Hannay, T., Stratford, K. & Jack, J. J. B. Presynaptic release probability influences the locus of long-term potentiation. Nature 360, 70–73 (1992).
Stevens, C. F. & Wang, Y. Changes in reliability of synaptic function as a mechanism for plasticity. Nature 371, 704–707 (1994).
Malgaroli, A. et al. Presynaptic component of long-term potentiation visualized at individual hippocampal synapses. Science 268, 1624–1628 (1995).
Malenka, R. C., Kauer, J. A., Zucker, R. S. & Nicoll, R. A. Postsynaptic calcium is sufficent for potentiation of hippocampal synaptic transmission. Science 242, 81–84 (1988).
Neveu, D. & Zucker, R. S. Long-lasting potentiation and depression without presynaptic activity. J. Neurophysiol. 75, 2157–2160 (1996).
Cash, S., Zucker, R. S. & Poo, M. M. Spread of synaptic depression mediated by presynaptic cytoplasmic signaling. Science 272, 998–1001 (1996).
Frotscher, M., Heimrich, B. & Schwegler, H. Plasticity of identified neurons in slice cultures of hippocampus: a combined Golgi/electron microscopic and immunocytochemical study. Prog. Brain Res. 83, 323–339 (1990).
Wolburg, H. & Bolz, J. Ultrastructural organization of slice cultures from rat visual cortex. J. Neurocytol. 20, 552–563 (1991).
Acknowledgements
We thank M. Häusser, M. Hübener and D. Madison for discussion and comments on the manuscript, and V. Staiger, D. Bühringer and G. Kreutzberg for help with some of the control experiments.
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Engert, F., Bonhoeffer, T. Synapse specificity of long-term potentiation breaks down at short distances. Nature 388, 279–284 (1997). https://doi.org/10.1038/40870
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DOI: https://doi.org/10.1038/40870
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