Spike Transmission Failures in Axons from Cortical Neurons

Overview

Journal iScience

Publisher Cell Press

Date 2024 Sep 30

PMID 39346673

Authors

Netanel Ofer

Victor Hugo Cornejo

Rafael Yuste

Affiliations

Soon will be listed here.

Abstract

The propagation of action potentials along axons is traditionally considered reliable due to the high safety factor for axonal spike transmission. However, numerical simulations suggest that high-frequency spikes could fail to invade distal axonal branches. To explore this experimentally , we used an axonal-targeted calcium indicator to image action potentials at axonal terminal branches in the superficial layers of mouse somatosensory cortical neurons. We activated axons with an extracellular electrode, varying stimulation frequencies, and analyzed the images to computationally extract axonal morphologies and associated calcium responses. We found that axonal boutons have higher calcium accumulations than their axonal shafts, as was reported . However, contrary to previous results, our data reveal spike failures at high spike frequencies in a significant subset of branches as a function of branching geometry. These findings suggest that axonal morphologies could contribute to signal processing in the cortex.

References

Goldstein S, RALL W . Changes of action potential shape and velocity for changing core conductor geometry. Biophys J. 1974; 14(10):731-57. PMC: 1334570. DOI: 10.1016/S0006-3495(74)85947-3. View

Johnson V, Stewart W, Smith D . Axonal pathology in traumatic brain injury. Exp Neurol. 2012; 246:35-43. PMC: 3979341. DOI: 10.1016/j.expneurol.2012.01.013. View

Gershoni-Emek N, Altman T, Ionescu A, Costa C, Gradus-Pery T, Willis D . Localization of RNAi Machinery to Axonal Branch Points and Growth Cones Is Facilitated by Mitochondria and Is Disrupted in ALS. Front Mol Neurosci. 2018; 11:311. PMC: 6134038. DOI: 10.3389/fnmol.2018.00311. View

Cho I, Panzera L, Chin M, Hoppa M . Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points. J Neurosci. 2017; 37(39):9519-9533. PMC: 6596771. DOI: 10.1523/JNEUROSCI.0891-17.2017. View

Pnevmatikakis E, Soudry D, Gao Y, Machado T, Merel J, Pfau D . Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data. Neuron. 2016; 89(2):285-99. PMC: 4881387. DOI: 10.1016/j.neuron.2015.11.037. View

Ali F, Kwan A . Interpreting calcium signals from neuronal cell bodies, axons, and dendrites: a review. Neurophotonics. 2019; 7(1):011402. PMC: 6664352. DOI: 10.1117/1.NPh.7.1.011402. View

Cichon J, Gan W . Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015; 520(7546):180-5. PMC: 4476301. DOI: 10.1038/nature14251. View

Hari K, Lucas-Osma A, Metz K, Lin S, Pardell N, Roszko D . GABA facilitates spike propagation through branch points of sensory axons in the spinal cord. Nat Neurosci. 2022; 25(10):1288-1299. PMC: 10042549. DOI: 10.1038/s41593-022-01162-x. View

de Kock C, Sakmann B . High frequency action potential bursts (>or= 100 Hz) in L2/3 and L5B thick tufted neurons in anaesthetized and awake rat primary somatosensory cortex. J Physiol. 2008; 586(14):3353-64. PMC: 2538819. DOI: 10.1113/jphysiol.2008.155580. View

10.

Manor Y, Koch C, Segev I . Effect of geometrical irregularities on propagation delay in axonal trees. Biophys J. 1991; 60(6):1424-37. PMC: 1260202. DOI: 10.1016/S0006-3495(91)82179-8. View

11.

Tomassy G, Berger D, Chen H, Kasthuri N, Hayworth K, Vercelli A . Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex. Science. 2014; 344(6181):319-24. PMC: 4122120. DOI: 10.1126/science.1249766. View

12.

Manoim J, Davidson A, Weiss S, Hige T, Parnas M . Lateral axonal modulation is required for stimulus-specific olfactory conditioning in Drosophila. Curr Biol. 2022; 32(20):4438-4450.e5. PMC: 9613607. DOI: 10.1016/j.cub.2022.09.007. View

13.

Hamada M, Popovic M, Kole M . Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons. Front Cell Neurosci. 2017; 11:45. PMC: 5326753. DOI: 10.3389/fncel.2017.00045. View

14.

Hodapp A, Kaiser M, Thome C, Ding L, Rozov A, Klumpp M . Dendritic axon origin enables information gating by perisomatic inhibition in pyramidal neurons. Science. 2022; 377(6613):1448-1452. DOI: 10.1126/science.abj1861. View

15.

Kasthuri N, Hayworth K, Berger D, Schalek R, Conchello J, Knowles-Barley S . Saturated Reconstruction of a Volume of Neocortex. Cell. 2015; 162(3):648-61. DOI: 10.1016/j.cell.2015.06.054. View

16.

Zang Y, Marder E . Interactions among diameter, myelination, and the Na/K pump affect axonal resilience to high-frequency spiking. Proc Natl Acad Sci U S A. 2021; 118(32). PMC: 8364126. DOI: 10.1073/pnas.2105795118. View

17.

Debanne D . Information processing in the axon. Nat Rev Neurosci. 2004; 5(4):304-16. DOI: 10.1038/nrn1397. View

18.

Foust A, Popovic M, Zecevic D, McCormick D . Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons. J Neurosci. 2010; 30(20):6891-902. PMC: 2990270. DOI: 10.1523/JNEUROSCI.0552-10.2010. View

19.

Vasu S, Kaphzan H . The role of axonal voltage-gated potassium channels in tDCS. Brain Stimul. 2022; 15(3):861-869. DOI: 10.1016/j.brs.2022.05.019. View

20.

Poirazi P, Brannon T, Mel B . Pyramidal neuron as two-layer neural network. Neuron. 2003; 37(6):989-99. DOI: 10.1016/s0896-6273(03)00149-1. View