LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite


Structural remodelling of synapses1,2,3,4 and formation of new synaptic contacts5,6,7,8 has been postulated as a possible mechanism underlying the late phase of long-term potentiation (LTP), a form of plasticity which is involved in learning and memory9. Here we use electron microscopy to analyse the morphology of synapses activated by high-frequency stimulation and identified by accumulated calcium in dendritic spines. LTP induction resulted in a sequence of morphological changes consisting of a transient remodelling of the postsynaptic membrane followed by a marked increase in the proportion of axon terminals contacting two or more dendritic spines. Three-dimensional reconstruction revealed that these spines arose from the same dendrite. As pharmacological blockade of LTP prevented these morphological changes, we conclude that LTP is associated with the formation of new, mature and probably functional synapses contacting the same presynaptic terminal and thereby duplicating activated synapses.

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Figure 1: Labelling of activated spine profiles by induction of LTP.
Figure 2: Time course of ultrastructural changes associated with LTP induction.
Figure 3: Blockade of LTP prevents morphological changes.
Figure 4: Three-dimensional reconstruction of multiple spine boutons.


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We thank L. M. Cruz-Orive for advice on stereology; K. Harris for 3D reconstruction software; D. Smithies for morphometry software on AVS; L. Parisi and M. Moosmayer for culture preparation and technical assistance; and F. Pillonel for photographic work. This work was supported by the Swiss National Science Foundation, the Human Frontier Science Program, the National Priority Program and the Jean-Falk Vairant Foundation.

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Correspondence to D. Muller.

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Toni, N., Buchs, PA., Nikonenko, I. et al. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425 (1999).

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