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Dendritic spikes as a mechanism for cooperative long-term potentiation

Abstract

Strengthening of synaptic connections following coincident pre- and postsynaptic activity was proposed by Hebb as a cellular mechanism for learning1. Contemporary models assume that multiple synapses must act cooperatively to induce the postsynaptic activity required for hebbian synaptic plasticity2,3,4,5. One mechanism for the implementation of this cooperation is action potential firing, which begins in the axon, but which can influence synaptic potentiation following active backpropagation into dendrites6. Backpropagation is limited, however, and action potentials often fail to invade the most distal dendrites7,8,9,10. Here we show that long-term potentiation of synapses on the distal dendrites of hippocampal CA1 pyramidal neurons does require cooperative synaptic inputs, but does not require axonal action potential firing and backpropagation. Rather, locally generated and spatially restricted regenerative potentials (dendritic spikes) contribute to the postsynaptic depolarization and calcium entry necessary to trigger potentiation of distal synapses. We find that this mechanism can also function at proximal synapses, suggesting that dendritic spikes participate generally in a form of synaptic potentiation that does not require postsynaptic action potential firing in the axon.

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Figure 1: Induction of long-term potentiation at distal synapses is independent of backpropagating action potentials.
Figure 2: LTP at distal synapses requires voltage-gated calcium channels and NMDA receptors.
Figure 3: Large theta-burst responses and distal calcium influx are associated with dendritic spikes.
Figure 4: Dendritic spikes contribute to LTP induction at stratum radiatum (SR) synapses.

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Acknowledgements

This work was supported by the National Institutes of Health.

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Correspondence to Nelson Spruston.

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Golding, N., Staff, N. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002). https://doi.org/10.1038/nature00854

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