Functional imaging of conduction dynamics in cortical and spinal axons
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Curated by eLife
eLife assessment
This work provides fundamental new insight into fine axonal morphologies based solely on extracellular action potential recordings. They provide compelling evidence of fine resolution in mapping functional connections between neurons. The work may have broad use in neurobiology, bioengineering, stem cell biology, as well as tissue engineering in functional characterization.
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Abstract
Mammalian axons are specialized for transmitting action potentials to targets within the central and peripheral nervous system. A growing body of evidence suggests that, besides signal conduction, axons play essential roles in neural information processing, and their malfunctions are common hallmarks of neurodegenerative diseases. The technologies available to study axonal function and structure integrally limit the comprehension of axon neurobiology. High-density microelectrode arrays (HD-MEAs) allow for accessing axonal action potentials at high spatiotemporal resolution, but provide no insights on axonal morphology. Here, we demonstrate a method for electrical visualization of axonal morphologies based on extracellular action potentials recorded from cortical and motor neurons using HD-MEAs. The method enabled us to reconstruct up to 5-cm-long axonal arbors and directly monitor axonal conduction across thousands of recording sites. We reconstructed 1.86 m of cortical and spinal axons in total and found specific features in their structure and function.
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eLife assessment
This work provides fundamental new insight into fine axonal morphologies based solely on extracellular action potential recordings. They provide compelling evidence of fine resolution in mapping functional connections between neurons. The work may have broad use in neurobiology, bioengineering, stem cell biology, as well as tissue engineering in functional characterization.
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Reviewer #1 (Public Review):
The authors developed a new approach to enable the reconstruction of fine axonal morphologies based solely on extracellular action potential recordings from in vitro mammalian neurons using a high-density microelectrode array system with an integrated CMOS camera. They provide compelling evidence of fine resolution in mapping functional connections between neurons via very fine axons. The advantage of the approach is that it provides a label-free electrical visualization of axon conduction trajectories as well as the ability to access the AP waveforms. The work may have broad use in neurobiology, bioengineering, stem cell biology, as well as tissue engineering in functional characterization.
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Reviewer #2 (Public Review):
This is a very interesting and compelling paper reporting a method for analyzing the features of action potential conduction in cortical and spinal neurons in vitro using high-density CMOS micro-electrode arrays. The authors report the performances of their detection algorithm allowing them to reconstruct the functional map of single-branching axons. In particular, they compare the functional conduction maps of cortical and spinal axons, and they show that spinal axons display larger spike signals in their distal part compared to cortical axons, but a lower number of branches. In addition, they reveal that spinal axons display a higher conduction velocity compared to cortical ones.
This study is particularly interesting as it constitutes a compelling methodological report of action potential propagation up …
Reviewer #2 (Public Review):
This is a very interesting and compelling paper reporting a method for analyzing the features of action potential conduction in cortical and spinal neurons in vitro using high-density CMOS micro-electrode arrays. The authors report the performances of their detection algorithm allowing them to reconstruct the functional map of single-branching axons. In particular, they compare the functional conduction maps of cortical and spinal axons, and they show that spinal axons display larger spike signals in their distal part compared to cortical axons, but a lower number of branches. In addition, they reveal that spinal axons display a higher conduction velocity compared to cortical ones.
This study is particularly interesting as it constitutes a compelling methodological report of action potential propagation up to 5-8 mm in single axons in vitro.
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