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This article is part of the supplement: Twentieth Annual Computational Neuroscience Meeting: CNS*2011

Open Access Oral presentation

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

Mark EJ Sheffield1, Tyler K Best1, Brett D Mensh2, William L Kath13* and Nelson Spruston1

Author Affiliations

1 Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA

2 Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA

3 Department of Applied Mathematics, Northwestern University, Evanston, Illinois 60208, USA

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BMC Neuroscience 2011, 12(Suppl 1):O17  doi:10.1186/1471-2202-12-S1-O17

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/12/S1/O17


Published:18 July 2011

© 2011 Sheffield et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oral presentation

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. In a subset of rodent hippocampal and neocortical interneurons in acute slices prepared from serotonin 5b receptor (Htr5b) BAC transgenic mice [1], we found a much slower form of integration leading to action potential initiation in the distal axon. In approximately 80% of these interneurons (n=214 of 274), and in 23% of hippocampal interneurons in wild-type C57BL/6 mice (n=6 of 26), hundreds of spikes, evoked over a period of minutes, resulted in persistent firing that lasted for a similar duration.

Persistent firing was observed in response to step current injections, synaptic stimulation, sine wave current injections or in response to stimulation with natural spike trains [2]. With all of these protocols, multiple stimuli were required to induce persistent firing. While axonal action potential firing was required to trigger persistent firing, somatic depolarization was not; antidromic stimulation of the axon while hyperpolarizing the soma with current injection produced persistent firing. In addition, phase plots of persistent firing revealed that spikes had two components: an initial component represented spiking in the axon and a second component that overlapped with the current-evoked spikes, indicative of a somato-dendritic spike following an initial, axonally initiated spike.

In some recordings (n = 11), partial spikes (spikelets) were observed during persistent firing. These spikelets overlapped the first component of the full-amplitude spikes, with the peak of the spikelets corresponding to an inflection on the rising phase seen in the full-amplitude spikes. These observations suggest that the first component of each action potential during persistent firing is an axonal spike, which sometimes fails to evoke a somato-dendritic spike. Furthermore, in some cells (n=3), spikelets were observed if the soma was hyperpolarized during persistent firing. These spikelets were smaller than those observed without hyperpolarization, suggesting that they are caused by propagation failures at a more distal axonal location.

Using a stylized computational model constructed with the NEURON simulation environment [3] of a branching axon attached to a soma, we simulated both small- and large amplitude spikelets, as well as full-amplitude spikes, by depolarizing a branch of the axon during somatic hyperpolarization. Large-amplitude spikelets corresponded to failure of the action potential to invade the soma, whereas small-amplitude spikelets corresponded to failures at the axon branches, 40 μm from the soma. Similar results were obtained with a full morphological model of a branching axonal arborization.

Additionally, in paired recordings, persistent firing was not restricted to the stimulated neuron; it could also be produced in the unstimulated cell (n=3). None of these pairs exhibited direct electrical coupling, and both glutamate and GABA receptors were blocked.

Consolidating these results suggests the existence of a previously unknown operational mode for some mammalian neurons. 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.

Acknowledgements

Grant support was provided by the US National Institutes of Health (NS-046064).

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