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Slow integration leads to persistent action potential firing in distal axons of coupled interneurons

Abstract

The conventional view of neurons is that synaptic inputs are integrated on a timescale of milliseconds to seconds in the dendrites, with action potential initiation occurring in the axon initial segment. We found a much slower form of integration that leads to action potential initiation in the distal axon, well beyond the initial segment. In a subset of rodent hippocampal and neocortical interneurons, hundreds of spikes, evoked over minutes, resulted in persistent firing that lasted for a similar duration. Although axonal action potential firing was required to trigger persistent firing, somatic depolarization was not. In paired recordings, persistent firing was not restricted to the stimulated neuron; it could also be produced in the unstimulated cell. Thus, these interneurons can slowly integrate spiking, share the output across a coupled network of axons and respond with persistent firing even in the absence of input to the soma or dendrites.

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Figure 1: Persistent firing in Htr5b interneurons.
Figure 2: In vivo firing patterns induce persistent firing.
Figure 3: Full-sized action potentials and large and small spikelets during persistent firing match antidromic full and partial spikes.
Figure 4: Simulation of small and large spikelets indicates failure of antidromic action potentials at different locations along the axon.
Figure 5: Persistent firing induced by antidromic stimulation and intercellular signaling.
Figure 6: Calcium effects on persistent firing.
Figure 7: Gap junction blockers inhibit persistent firing.

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Acknowledgements

We thank T. Klausberger, S. Layton and M. Wilson for providing in vivo spiking data, and M. Benton, M. Nusbaum and members of the Spruston laboratory for helpful discussion and comments on the manuscript. We also thank E. Grodinsky for interneuron reconstructions. Grant support was provided by the US National Institutes of Health (NS-046064 to N.S. and W.L.K.) and the National Alliance for Research on Schizophrenia and Depression (N.S.). M.E.J.S. was supported by a Presidential Fellowship from Northwestern University.

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Authors

Contributions

All authors participated in the design of the experiments and the analysis and interpretation of the data. M.E.J.S. and T.K.B. performed the experiments. W.L.K. performed the simulations. N.S. and B.D.M. wrote the manuscript with input from the other authors.

Corresponding author

Correspondence to Nelson Spruston.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 and Supplementary Table 1 (PDF 5441 kb)

Supplementary Movie 1

Simple model of axonal action potential propagation in a stylized axon. (MOV 5750 kb)

Supplementary Movie 2

Model of axonal action potential propagation in a full morphological model. (MOV 11319 kb)

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Sheffield, M., Best, T., Mensh, B. et al. Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. Nat Neurosci 14, 200–207 (2011). https://doi.org/10.1038/nn.2728

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