Axon Neurobiology: Fine-Scale Dynamics of Microstructure and Function

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Coupling modalities between axons. (A) Three types of synapse-mediated coupling: through axo-axonal gap junctions (left), ephaptic coupling (middle), and chemical axonic synapses (right). (B) Indirect coupling via myelinating cells.
Review
18 September 2019
Axonal Computations
Pepe Alcami
 and 
Ahmed El Hady
12,464 views
27 citations
22,264 views
67 citations

Currently, a scientific debate is ongoing about modeling nerve impulse propagation. One of the models discussed is the celebrated Hodgkin-Huxley model of the action potential, which is central to the electricity-centered conception of the nerve impulse that dominates contemporary neuroscience. However, this model cannot represent the nerve impulse completely, since it does not take into account non-electrical manifestations of the nerve impulse for which there is ample experimental evidence. As a result, alternative models of nerve impulse propagation have been proposed in contemporary (neuro)scientific literature. One of these models is the Heimburg-Jackson model, according to which the nerve impulse is an electromechanical density pulse in the neural membrane. This model is usually contrasted with the Hodgkin-Huxley model and is supposed to potentially be able to replace the latter. However, instead of contrasting these models of nerve impulse propagation, another approach integrates these models in a general unifying model. This general unifying model, the Engelbrecht model, is developed to unify all relevant manifestations of the nerve impulse and their interaction(s). Here, we want to contribute to the debate about modeling nerve impulse propagation by conceptually analyzing the Engelbrecht model. Combining the results of this conceptual analysis with insights from philosophy of science, we make recommendations for the study of nerve impulse propagation. The first conclusion of this analysis is that attempts to develop models that represent the nerve impulse accurately and completely appear unfeasible. Instead, models are and should be used as tools to study nerve impulse propagation for varying purposes, representing the nerve impulse accurately and completely enough to achieve the specified goals. The second conclusion is that integrating distinct models into a general unifying model that provides a consistent picture of nerve impulse propagation is impossible due to the distinct purposes for which they are developed and the conflicting assumptions these purposes often require. Instead of explaining nerve impulse propagation with a single general unifying model, it appears advisable to explain this complex phenomenon using a ‘mosaic’ framework of models in which each model provides a partial explanation of nerve impulse propagation.

12,334 views
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Mini Review
26 April 2019
Technologies to Study Action Potential Propagation With a Focus on HD-MEAs
Vishalini Emmenegger
2 more and 
Andreas Hierlemann

Axons convey information in neuronal circuits via reliable conduction of action potentials (APs) from the axon initial segment (AIS) to the presynaptic terminals. Recent experimental findings increasingly evidence that the axonal function is not limited to the simple transmission of APs. Advances in subcellular-resolution recording techniques have shown that axons display activity-dependent modulation in spike shape and conduction velocity, which influence synaptic strength and latency. We briefly review here, how recent methodological developments facilitate the understanding of the axon physiology. We included the three most common methods, i.e., genetically encoded voltage imaging (GEVI), subcellular patch-clamp and high-density microelectrode arrays (HD-MEAs). We then describe the potential of using HD-MEAs in studying axonal physiology in more detail. Due to their robustness, amenability to high-throughput and high spatiotemporal resolution, HD-MEAs can provide a direct functional electrical readout of single cells and cellular ensembles at subcellular resolution. HD-MEAs can, therefore, be employed in investigating axonal pathologies, the effects of large-scale genomic interventions (e.g., with RNAi or CRISPR) or in compound screenings. A combination of extracellular microelectrode arrays (MEAs), intracellular microelectrodes and optical imaging may potentially reveal yet unexplored repertoires of axonal functions.

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