Neuron Morphology Influences Axon Initial Segment Plasticity

Gulledge, Allan T.; Bravo, Jaime J.

doi:10.1523/eneuro.0085-15.2016

Cited by 84 publications

(91 citation statements)

References 44 publications

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“…Rather than reducing intrinsic excitability, our modeling predicts that shifting the AIS alone distally would weakly promote axonal firing (Fig. 5), consistent with theoretical and modeling results (9,11). Furthermore, our results indicate that, in cortical pyramidal cells, the anatomical location of the AIS is to a large degree covarying with the local somatodendritic membrane area, ensuring the generation of uniform somatic APs in the face of highly variable dendritic loads.…”

Section: Discussionsupporting

confidence: 85%

“…Experimental studies showed that an activity-dependent distal shift of the AIS is associated with decreased AP output (5). In contrast, model simulations showed that shifting the AIS distally promotes excitability (9). One of the critical factors influencing AIS excitability is the large somatodendritic membrane area acting as current sink for sodium current generated in the AIS (10)(11)(12).…”

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confidence: 99%

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Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Hamada

Goethals

Vries

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

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In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not wellunderstood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.T he axon initial segment (AIS) specifies in vertebrate neurons a single domain for the final integration of synaptic input and the initiation of action potentials (APs) (1, 2). To rapidly produce large inward and outward currents mediating the AP, the AIS contains a complex arrangement of cytoskeletal and transmembrane proteins clustering high densities of voltage-gated sodium (Nav) and potassium (Kv) channels in the axolemma (2-4). Although the composition of ion channels is critical for initiation and regulation of firing patterns, there are emerging insights that the AIS is not operating in isolation but is also subject to activity-dependent changes in size and location constrained by the local dendritic branch geometry and the passive cable properties (5-7). Experimental studies linking changes in AIS length and neuronal output showed that an increased length facilitates AP generation (6,8). In these cases, the net increased excitability is a logical consequence of the larger Nav conductance. However, predicting the impact of AIS location on neuronal output is more complex. Experimental studies showed that an activity-dependent distal shift of the AIS is associated with decreased AP output (5). In contrast, model simulations showed that shifting the AIS distally promotes excitability (9). One of the critical factors influencing AIS excitability is the large somatodendritic membrane area acting as current sink for sodium current generated in the AIS (10-12). In this view, a distal anatomical location of the AIS increases electrical compartmentalization and facilitates axonal AP generation. Indeed, the local depolarization in the...

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Hamada

Goethals

Vries

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

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“…Thus, a negative correlation between the AIS length and distance from the soma can maximize excitability, and this relationship is critically influenced by the conductances at both the AIS and the somato-dendritic compartments. The importance of somato-dendritic compartments to this relationship is also reported in models with realistic neuronal morphologies (Gulledge and Bravo, 2016). …”

Section: Structural Effects On Excitabilitysupporting

confidence: 53%

Structural and Functional Plasticity at the Axon Initial Segment

Yamada

Kuba

2016

Front. Cell. Neurosci.

133

127

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The axon initial segment (AIS) is positioned between the axonal and somato-dendritic compartments and plays a pivotal role in triggering action potentials (APs) and determining neuronal output. It is now widely accepted that structural properties of the AIS, such as length and/or location relative to the soma, change in an activity-dependent manner. This structural plasticity of the AIS is known to be crucial for homeostatic control of neuronal excitability. However, it is obvious that the impact of the AIS on neuronal excitability is critically dependent on the biophysical properties of the AIS, which are primarily determined by the composition and characteristics of ion channels in this domain. Moreover, these properties can be altered via phosphorylation and/or redistribution of the channels. Recently, studies in auditory neurons showed that alterations in the composition of voltage-gated K+ (Kv) channels at the AIS coincide with elongation of the AIS, thereby enhancing the neuronal excitability, suggesting that the interaction between structural and functional plasticities of the AIS is important in the control of neuronal excitability. In this review, we will summarize the current knowledge regarding structural and functional alterations of the AIS and discuss how they interact and contribute to regulating the neuronal output.

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“…Regardless of the mechanism employed, both of these structural forms of AIS plasticity appear to serve a homeostatic purpose, bringing the cell's excitation levels closer to the state before the manipulation. It is important to note, however, that the effect of changes in AIS position on excitability are likely to depend on the cell type or model used [60]. A study of L5 cortical neurons showed that AP initiation occurred in the distal portion of the AIS, as this was sufficiently distant from the large conductive and capacitive load of the soma and dendrites [55].…”

Section: The Aismentioning

confidence: 99%

“…However, myelination is strongly variable [62] and many cell types, including hippocampal pyramidal cells in culture, have largely unmyelinated axons and much smaller cell bodies. This could possibly explain why in some cases the dissipation of current along the axonal membrane outweighs the uncoupling from the somatodendritic current sink [60], such that a distal shift of the AIS can decrease excitability instead [52]. In any case, this strongly argues for an important contribution of structural parameters such as axon diameter, soma size, and, of course, AIS length and location to neuronal output generation.…”

Section: The Aismentioning

confidence: 99%

Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs

Wefelmeyer

Puhl

Burrone

2016

Trends in Neurosciences

108

103

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Neurons in the brain are highly plastic, allowing an organism to learn and adapt to its environment. However, this ongoing plasticity is also inherently unstable, potentially leading to aberrant levels of circuit activity. Homeostatic forms of plasticity are thought to provide a means of controlling neuronal activity by avoiding extremes and allowing network stability. Recent work has shown that many of these homeostatic modifications change the structure of subcellular neuronal compartments, ranging from changes to synaptic inputs at both excitatory and inhibitory compartments to modulation of neuronal output through changes at the axon initial segment (AIS) and presynaptic terminals. Here we review these different forms of structural plasticity in neurons and the effects they may have on network function.

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Neuron Morphology Influences Axon Initial Segment Plasticity

Abstract: Visual Abstract

Cited by 84 publications

References 44 publications

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

Structural and Functional Plasticity at the Axon Initial Segment

Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs

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