Theoretical relation between axon initial segment geometry and excitability

Goethals, Sarah; Brette, Romain

doi:10.7554/elife.53432

Cited by 55 publications

(99 citation statements)

References 87 publications

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“…In M1LV neurons, age-related changes of both parameters occurred in the period of most prominent AIS elongation. These changes aligned with predicted effects of AIS elongation and likely contributed to optimal input-output conversion in growing neurons, according to the known relationship between optimal AIS length and cell size [12,13].…”

Section: Discussionsupporting

confidence: 67%

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Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons

Benedetti

Dannehl

Janssen

et al. 2020

IJMS

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Rodent neocortical neurons undergo prominent postnatal development and maturation. The process is associated with structural and functional maturation of the axon initial segment (AIS), the site of action potential initiation. In this regard, cell size and optimal AIS length are interconnected. In sensory cortices, developmental onset of sensory input and consequent changes in network activity cause phasic AIS plasticity that can also control functional output. In non-sensory cortices, network input driving phasic events should be less prominent. We, therefore, explored the relationship between postnatal functional maturation and AIS maturation in principal neurons of the primary motor cortex layer V (M1LV), a non-sensory area of the rat brain. We hypothesized that a rather continuous process of AIS maturation and elongation would reflect cell growth, accompanied by progressive refinement of functional output properties. We found that, in the first two postnatal weeks, cell growth prompted substantial decline of neuronal input resistance, such that older neurons needed larger input current to reach rheobase and fire action potentials. In the same period, we observed the most prominent AIS elongation and significant maturation of functional output properties. Alternating phases of AIS plasticity did not occur, and changes in functional output properties were largely justified by AIS elongation. From the third postnatal week up to five months of age, cell growth, AIS elongation, and functional output maturation were marginal. Thus, AIS maturation in M1LV is a continuous process that attunes the functional output of pyramidal neurons and associates with early postnatal development to counterbalance increasing electrical leakage due to cell growth.

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Section: Discussionsupporting

confidence: 67%

“…However, the influence of different sodium channel isoforms on the voltage sensitivity of the AP threshold is debatable [23]. Conversely, IS component maturation, SD component maturation, and prominent AIS elongation adequately explain AP threshold hyperpolarization as supported by in silico models [12,13].…”

Section: Discussionmentioning

confidence: 97%

Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons

Benedetti

Dannehl

Janssen

et al. 2020

IJMS

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“…Resistive coupling theory provides a quantitative estimate of the axial current as a function of AIS geometry and g, by assuming that current entering the axonal membrane flows resistively towards the soma, which acts as a current sink (Brette, 2013;Hamada et al, 2016;Kole & Brette, 2018;Goethals & Brette, 2020). Suppose first that conductance density is very high, such that the AIS is clamped at ENa when sodium channels open (Fig.…”

Section: Axial Current and Ais Geometrymentioning

confidence: 99%

Electrical match between initial segment and somatodendritic compartment for action potential backpropagation in retinal ganglion cells

Goethals

Sierksma

Nicol

et al. 2020

Preprint

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The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ∼30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.

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“…For the models to more fully capture electrophysiological responses, one could consider using these models to build new model populations, but now with calcium currents rather than I h as the focused question (Sekulić and Skinner, 2018 ). It would also be helpful to acquire data on axonal properties of OLM cells beyond Martina et al ( 2000 ) to figure out their properties, and new theoretical insights could perhaps be harnessed (Goethals and Brette, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Integration of Within-Cell Experimental Data With Multi-Compartmental Modeling Predicts H-Channel Densities and Distributions in Hippocampal OLM Cells

Sekulić

Garrett

et al. 2020

Front. Cell. Neurosci.

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Theoretical relation between axon initial segment geometry and excitability

Cited by 55 publications

References 87 publications

Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons

Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons

Electrical match between initial segment and somatodendritic compartment for action potential backpropagation in retinal ganglion cells

Integration of Within-Cell Experimental Data With Multi-Compartmental Modeling Predicts H-Channel Densities and Distributions in Hippocampal OLM Cells

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