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Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons

Nature Neuroscience volume 8, pages 1667–1676 (2005)Cite this article

Abstract

The perforant-path projection to the hippocampus forms synapses in the apical tuft of CA1 pyramidal neurons. We used computer modeling to examine the function of these distal synaptic inputs, which led to three predictions that we confirmed in experiments using rat hippocampal slices. First, activation of CA1 neurons by the perforant path is limited, a result of the long distance between these inputs and the soma. Second, activation of CA1 neurons by the perforant path depends on the generation of dendritic spikes. Third, the forward propagation of these spikes is unreliable, but can be facilitated by modest activation of Schaffer-collateral synapses in the upper apical dendrites. This 'gating' of dendritic spike propagation may be an important activation mode of CA1 pyramidal neurons, and its modulation by neurotransmitters or long-term, activity-dependent plasticity may be an important feature of dendritic integration during mnemonic processing in the hippocampus.

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Figure 1: Strong and weak dendritic excitability models of CA1 pyramidal neurons respond differently to perforant-path activation.
Figure 2: Modes of activation of CA1 pyramidal neurons by perforant-path and Schaffer-collateral activation.
Figure 3: Gating of perforant-path–evoked dendritic spikes by Schaffer-collateral evoked EPSPs.
Figure 4: Dependence of PP-evoked dendritic spike propagation on the strength and timing of SC activation.
Figure 5: Mechanisms of conditional dendritic spike propagation.
Figure 6: Experimental perforant-path stimulus-response plot.
Figure 7: Dendritic spikes underlie perforant-path–evoked action potentials.
Figure 8: Coincident Schaffer-collateral stimulation increases spikelet frequency in response to perforant-path stimulation.

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Acknowledgements

We thank members of the Spruston and Kath labs and B. Mel for discussions. This work was supported by the US National Institutes of Health (NS-35180 to N.S., NS-46064 to N.S. and W.L.K., and NS-045437 to T.J.) and by the National Science Foundation (DGE-9987577 to A.R.).

Author information

Author notes

  1. Tim Jarsky and Alex Roxin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, 2205 Tech Drive, Evanston, 60208, Illinois, USA

    Tim Jarsky, William L Kath & Nelson Spruston

  2. Department of Engineering Science and Applied Mathematics, Northwestern University, 2145 Sheridan Road, Evanston, 60208, Illinois, USA

    Alex Roxin & William L Kath

  3. Unité Mixte de Recherche 8119, Centre Nationale de la Recherche Scientifique, Neurophysics and Physiology, Université René Descartes, 45 Rue des Saints Pères, Paris, 75270 Cedex 06, France

    Alex Roxin

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Correspondence to Nelson Spruston.

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Supplementary information

Supplementary Fig. 1

Successful forward propagation of dendritic spikes in strong dendritic excitability models (model cells 1 and 2, with animations). (PDF 709 kb)

Supplementary Fig. 2

Gating of PP-evoked dendritic spikes by SC EPSPs (model cell 1, with animations). (PDF 846 kb)

Supplementary Fig.3

Gating of PP-evoked dendritic spikes by SC EPSPs (model cell 2, with animations). (PDF 1246 kb)

Supplementary Fig. 4

Gating of PP-evoked dendritic spikes by SC EPSPs (model cell 3). (PDF 646 kb)

Supplementary Fig. 5

Bidirectional gating of dendritic spike propagation by excitation and feed-forward inhibition. (PDF 241 kb)

Supplementary Video 1 (GIF 200 kb)

Supplementary Video 2 (GIF 209 kb)

Supplementary Video 3 (GIF 107 kb)

Supplementary Video 4 (GIF 80 kb)

Supplementary Video 5 (GIF 197 kb)

Supplementary Video 6 (GIF 122 kb)

Supplementary Video 7 (GIF 86 kb)

Supplementary Video 8 (GIF 199 kb)

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Jarsky, T., Roxin, A., Kath, W. et al. Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons. Nat Neurosci 8, 1667–1676 (2005). https://doi.org/10.1038/nn1599

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