The role of axonal voltage-gated potassium channels in tDCS

Vasu, Sreerag Othayoth; Kaphzan, Hanoch

doi:10.1016/j.brs.2022.05.019

Cited by 9 publications

(9 citation statements)

References 63 publications

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“…Thus, the geometry of the axonal branches may modulate the firing pattern of action potential trains, which is essential for neuronal processing in health and disease. Moreover, axons are also highly sensitive and vulnerable components that are prone to damage, which can further impede spike propagation in cases of traumatic brain injury, stroke, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Parkinson’s ( Johnson et al, 2013 ; Tennant et al, 2017 ; Gershoni-Emek et al, 2018 ; Vasu and Kaphzan, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Spike transmission failures in axons from mouse cortical pyramidal neurons in vivo

Ofer,

Cornejo,

Yuste

2024

Preprint

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The propagation of action potentials along axons is traditionally considered to be reliable, as a consequence of the high safety factor of action potential propagation. However, numerical simulations have suggested that, at high frequencies, spikes could fail to invade distal axonal branches. Given the complex morphologies of axonal trees, with extensive branching and long-distance projections, spike propagation failures could be functionally important. To explore this experimentally in vivo, we used an axonal-targeted calcium indicator to image action potentials at axonal terminal branches in superficial layers from mouse somatosensory cortical pyramidal neurons. We activated axons with an extracellular electrode, varying stimulation frequencies, and computationally extracted axonal morphologies and associated calcium responses. We find that axonal boutons have higher calcium accumulations than their parent axons, as was reported in vitro. But, contrary to previous in vitro results, our data reveal spike failures in a significant subset of branches, as a function of branching geometry and spike frequency. The filtering is correlated with the geometric ratio of the branch diameters, as expected by cable theory. These findings suggest that axonal morphologies contribute to signal processing in the cortex.

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Section: Discussionmentioning

confidence: 99%

Spike transmission failures in axons from mouse cortical pyramidal neurons in vivo

Ofer,

Cornejo,

Yuste

2024

Preprint

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“…Considering the high heritability and persistent nature of mathematical disabilities ( 25 , 26 ), our study highlights a potential future research avenue in the neuropathology of dyscalculia ( 73 , 74 ). Moreover, because noninvasive brain stimulation techniques can alter potassium conductance ( 75 ), our findings may also inspire the development of innovative brain stimulation strategies to remediate learning difficulties, moving beyond traditional behavioral interventions. Together, these findings illuminate the transcriptomic and molecular correlates of the MAIP, enriching our understanding of the biological mechanisms underlying mathematical abilities.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical, transcriptomic, and molecular correlates of math ability and their prognostic value for predicting learning outcomes

Liu,

Supekar,

El-Said

et al. 2024

Sci. Adv.

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Foundational mathematical abilities, acquired in early childhood, are essential for success in our technology-driven society. Yet, the neurobiological mechanisms underlying individual differences in children’s mathematical abilities and learning outcomes remain largely unexplored. Leveraging one of the largest multicohort datasets from children at a pivotal stage of knowledge acquisition, we first establish a replicable mathematical ability–related imaging phenotype (MAIP). We then show that brain gene expression profiles enriched for candidate math ability–related genes, neuronal signaling, synaptic transmission, and voltage-gated potassium channel activity contributed to the MAIP. Furthermore, the similarity between MAIP gene expression signatures and brain structure, acquired before intervention, predicted learning outcomes in two independent math tutoring cohorts. These findings advance our knowledge of the interplay between neuroanatomical, transcriptomic, and molecular mechanisms underlying mathematical ability and reveal predictive biomarkers of learning. Our findings have implications for the development of personalized education and interventions.

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“…Experiments in cortical and hippocampal slices found evidence of acute changes in synaptic efficacy that are strongest with E-field aligned with the activated axonal inputs [ 13 , 26 ]. Using slices from motor cortex, Vasu and Kaphzan also reported changes in the rate of spontaneous vesicle release by dc stimulation, dependent on voltage-gated sodium, potassium, and calcium channels [ 68 – 70 ], suggesting modulation of presynaptic release machinery. However, electrophysiological measures of synaptic transmission include the influence of postsynaptic mechanisms, and the effects of dc stimulation on action potential-evoked presynaptic release have yet to be measured.…”

Section: Discussionmentioning

confidence: 99%

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry

Aberra,

Wang,

Grill

et al. 2023

Brain Stimulation

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The role of axonal voltage-gated potassium channels in tDCS

Cited by 9 publications

References 63 publications

Spike transmission failures in axons from mouse cortical pyramidal neurons in vivo

Spike transmission failures in axons from mouse cortical pyramidal neurons in vivo

Neuroanatomical, transcriptomic, and molecular correlates of math ability and their prognostic value for predicting learning outcomes

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry

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