Plasticity of the Axonal Trigger Zone

Adachi, Ryota; Yamada, Ryūji; Kuba, Hiroshi

doi:10.1177/1073858414535986

Cited by 32 publications

(41 citation statements)

References 61 publications

(84 reference statements)

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“…The adaptive mechanisms include synaptic scaling, changes in the number of synapses or dendritic excitability (2)(3)(4)(5)(6), and structural and functional alterations of the axon initial segment (AIS) (7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment

Lezmy

Lipinsky

Khrapunsky

et al. 2017

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

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Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K + channels, which predominantly localize to the AIS and are essential for tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made neurons more excitable, minutes to hours of sustained M-current depression resulted in a gradual reduction in intrinsic excitability. Dual soma-axon patch-clamp recordings combined with axonal Na + imaging and immunocytochemistry revealed that these compensatory alterations were associated with a distal shift of the spike trigger zone and distal relocation of FGF14, Na + , and K v 7 channels but not ankyrin G. The concomitant distal redistribution of FGF14 together with Na v and K v 7 segments along the AIS suggests that these channels relocate as a structural and functional unit. These fast homeostatic changes were independent of L-type Ca 2+ channel activity but were contingent on the crucial AIS protein, protein kinase CK2. Using compartmental simulations, we examined the effects of varying the AIS position relative to the soma and found that AIS distal relocation of both Na v and K v 7 channels elicited a decrease in neuronal excitability. Thus, alterations in M-channel activity rapidly trigger unique AIS plasticity to stabilize network excitability.homeostatic plasticity | axon initial segment | M-current | potassium channel | K v 7

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mentioning

confidence: 99%

M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment

Lezmy

Lipinsky

Khrapunsky

et al. 2017

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

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“…3 Recently, the AIS has been shown to be not only a platform to lock channels in high density, but to be a dynamic structure that tunes neuronal excitability. 1,61,76 Depending on the spacing between cell body and the proximal end of the AIS, as well as the total length of the AIS, neurons can shift their action potential threshold up and down within a couple of hours. 48 The density and kinetic properties of Na V channels and voltage-gated potassium channels (K V ) contribute to the fine-tuning of the action potential threshold as a response to changes in network activity.…”

Section: Na V Channelsmentioning

confidence: 99%

“…Whereas chronic bursting activity moves the AIS away from the soma, a loss of sensory input leads to an enlargement of the AIS, resulting in a higher or lower threshold for the initiation of an action potential, respectively. 1,61,76 The tuning of the action potential threshold is critically dependent on the activity of voltage-gated calcium channels and the density and kinetic properties of Na V and K V channels. 1,77 Crucial questions, such as how channels are inserted into and removed from membranes and whether there are density gradients in Na v and K v channel expression along the AIS, can now be answered with the observation of channel dynamics in the membrane.…”

Section: Na V Channelsmentioning

confidence: 99%

“…1,61,76 The tuning of the action potential threshold is critically dependent on the activity of voltage-gated calcium channels and the density and kinetic properties of Na V and K V channels. 1,77 Crucial questions, such as how channels are inserted into and removed from membranes and whether there are density gradients in Na v and K v channel expression along the AIS, can now be answered with the observation of channel dynamics in the membrane. Interestingly, both ion channel populations (Na V and K V ) are linked to the Ankyrin G scaffold via similar binding motifs.…”

Section: Na V Channelsmentioning

confidence: 99%

“…18 Alterations to ion channel composition and AIS size are known mechanisms of neuronal excitability tuning. 1,77 It remains to be explored whether the surface dynamics of Na V and K V channels contribute to such alterations in AIS size or position.…”

Section: Na V Channelsmentioning

confidence: 99%

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et al. 2016

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Neurons encode information in fast changes of the membrane potential, and thus electrical membrane properties are critically important for the integration and processing of synaptic inputs by a neuron. These electrical properties are largely determined by ion channels embedded in the membrane. The distribution of most ion channels in the membrane is not spatially uniform: they undergo activity-driven changes in the range of minutes to days. Even in the range of milliseconds, the composition and topology of ion channels are not static but engage in highly dynamic processes including stochastic or activity-dependent transient association of the pore-forming and auxiliary subunits, lateral diffusion, as well as clustering of different channels. In this review we briefly discuss the potential impact of mobile sodium, calcium and potassium ion channels and the functional significance of this for individual neurons and neuronal networks.

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The emerging functions of oligodendrocytes in regulating neuronal network behaviour

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2014

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Myelin is required for efficient nerve conduction, but not all axons are myelinated to the same extent. Here we review recent studies that have revealed distinct myelination patterns of different axonal paths, suggesting that myelination is not an all or none phenomenon and that its presence is finely regulated in central nervous system networks. Whereas powerful reductionist biology has led to important knowledge of how oligodendrocytes function by themselves, little is known about their role in neuronal networks. We still do not understand how oligodendrocytes integrate information from neurons to adapt their function to the need of the system. An intricate cross talk between neurons and glia is likely to exist and to determine how neuronal circuits operate as a whole. Dissecting these mechanisms by using integrative systems biology approaches is one of the major challenges ahead.

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Plasticity of the Axonal Trigger Zone

Cited by 32 publications

References 61 publications

M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment

M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment

Surface dynamics of voltage-gated ion channels

The emerging functions of oligodendrocytes in regulating neuronal network behaviour

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