Neuronal adaptation involves rapid expansion of the action potential initiation site

Scott, Ricardo; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

doi:10.1038/ncomms4817

Cited by 23 publications

(32 citation statements)

References 54 publications

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“…Converging lines of evidence suggest that the AIS is a highly dynamic structure, exhibiting structural plasticity over different timescales ranging from a few hours to several days (7)(8)(9)(10)(11)(12)(13)(29)(30)(31). Various elegant studies used typical triggers of plasticity such as sensory deprivation, optogenetic stimulation, or high-K + -induced depolarization (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…Long considered to be the trigger zone for AP initiation (28), the AIS was regarded as a static and rigid structure encompassing ion channels anchored to a scaffolding and cytoskeletal protein network. Now, it is recognized that the AIS is a highly dynamic structure, capable of structural and functional plasticity and continuously adapting to changes in neuronal activity (8,12,(29)(30)(31). In 2010, two seminal studies found that changes in neuronal activity could lead to AIS relocation or resizing as a new mechanism of slow homeostatic adaptation (32,33).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…This inactivation decreases with increasing distance from the soma, due to an electrotonic decrement of the depolarization. Accordingly, neurons overcome the effects of this inactivation and maintain their excitability by transient expansion of AP initiation areas at the AIS (hippocampus, Scott et al, 2014), or by localizing the AIS at a distal location (nucleus laminaris, see above, Kuba et al, 2006). …”

Section: Modulation Via Ionotropic Receptorsmentioning

confidence: 99%

Structural and Functional Plasticity at the Axon Initial Segment

Yamada

Kuba

2016

Front. Cell. Neurosci.

122

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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“…First, it may extend the spike initiation site to a wider axonal zone (Scott et al, 2014). But most importantly, it will largely modulate the amplitude of the action potential in the axon upon changes in membrane potential in the cell body (Rama et al, 2015a).…”

Section: Hyperpolarization-induced Ad Facilitation (H-adf)mentioning

confidence: 99%

Dynamic Control of Neurotransmitter Release by Presynaptic Potential

Zbili

Rama

Debanne

2016

Front. Cell. Neurosci.

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Action potentials (APs) in the mammalian brain are thought to represent the smallest unit of information transmitted by neurons to their postsynaptic targets. According to this view, neuronal signaling is all-or-none or digital. Increasing evidence suggests, however, that subthreshold changes in presynaptic membrane potential before triggering the spike also determines spike-evoked release of neurotransmitter. We discuss here how analog changes in presynaptic voltage may regulate spike-evoked release of neurotransmitter through the modulation of biophysical state of voltage-gated potassium, calcium and sodium channels in the presynaptic compartment. The contribution of this regulation has been greatly underestimated and we discuss the impact for information processing in neuronal circuits.

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Neuronal adaptation involves rapid expansion of the action potential initiation site

Cited by 23 publications

References 54 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

Structural and Functional Plasticity at the Axon Initial Segment

Dynamic Control of Neurotransmitter Release by Presynaptic Potential

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