Plasticity of the Axon Initial Segment: Fast and Slow Processes with Multiple Functional Roles

Petersen, Anders Victor; Cotel, Florence; Perrier, Jean‐François

doi:10.1177/1073858416648311

Cited by 31 publications

(30 citation statements)

References 83 publications

(130 reference statements)

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“…Depending on the excitation state of the neuronal network both in vitro and in vivo, individual neurons can undergo structural and/or functional AIS plasticity, including modulation of channel density or composition, to adapt to or strengthen the changes in synaptic drive ((Bender et al, 2010;Benned-Jensen et al, 2016;Lezmy et al, 2017;Muir and Kittler, 2014); reviewed in (Jamann et al, 2018;Petersen et al, 2016)). For example, triggering chronic depolarization in neuronal networks in vitro (Evans et al, 2015;Grubb and Burrone, 2010) or using a complete and irrevocable elimination of sensory input in vivo (Kuba et al, 2010) led to significant geometrical and functional AIS changes.…”

Section: Introductionmentioning

confidence: 99%

Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

Jamann

Dannehl

Wagener

et al. 2020

Preprint

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The axon initial segment (AIS) is an important axonal microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent cortical plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using an in vivo model of the mouse whisker-to-barrel pathway in combination with immunofluorescence, confocal analysis and patch-clamp electrophysiological recordings, we observed bidirectional AIS plasticity. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal inputoutput relations.

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Section: Introductionmentioning

confidence: 99%

Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

Jamann

Dannehl

Wagener

et al. 2020

Preprint

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“…Axon initial segment (AIS) is an excitable neuronal domain positioned between the axonal and somato-dendritic compartment, which is involved in action potential initiation and fine-tunes the excitability of neurons (11). In recent years, our understanding of the molecular structure of AIS, its structural and functional plasticity related to the excitability of neurons, has seen major advances (12,13).…”

Section: Introductionmentioning

confidence: 99%

Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats

Liu

Feng

Liu

et al. 2017

Molecular Medicine Reports

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Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly-generated neurons that are involved in recurrent seizures following pilocarpine-induced status epilepticus (SE). The present study first established a pilocarpine-induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX). AIS plasticity alterations include length and distance from soma in the hippocampal newly-generated neurons post-SE. The results of the present study demonstrated that pilocarpine-induced epileptic rats exhibited aberrant hippocampal neurogenesis and longer DCX-labeled cell dendrites in the dentate gyrus. Pilocarpine-induced epileptic rats demonstrated shortened lengths of AIS and an increased distance from the soma in hippocampal newborn neurons. Mibefradil, a T/L-type calcium blocker, reversed the alterations in length and position of AIS in hippocampal newborn neurons post-SE, accompanied by decreased long-term seizure activity without increased aberrant neurogenesis. These findings indicate that the plasticity of AIS in hippocampal neurogenesis may have profound consequences in epilepsy, at least in animals.

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“…Besides passive and voltage-dependent conductances, intrinsic excitability is tightly regulated by the site of spike initiation in the axon initial segment (AIS) (Araki and Otani, 1955; Bean, 2007; Bender and Trussell, 2012; Coombs et al, 1957; Debanne et al, 2011; Grubb and Burrone, 2010a; Kole and Stuart, 2012; Petersen et al, 2016; Scott et al, 2014; Wefelmeyer et al, 2016). When it is recorded at the somatic level, AP waveform generally comprises two distinct components (Colbert and Johnston, 1996; Coombs et al, 1957; Fuortes et al, 1957; Grace and Bunney, 1983; Häusser et al, 1995), the first peak reflecting the spike initiation in AIS and the second peak the somato-dendritic spike (Bean, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…These data, that suggested a change in the axonal component of the AP waveform, could result from a structural modification of AIS. The AIS is a key element involved in the regulation of neuronal excitability since this cellular compartment is responsible for action potential initiation (Araki and Otani, 1955; Bean, 2007; Bender and Trussell, 2012; Coombs et al, 1957; Debanne et al, 2011; Grubb and Burrone, 2010a; Kole and Stuart, 2012; Petersen et al, 2016; Scott et al, 2014; Wefelmeyer et al, 2016). Moreover, it is now well accepted that AIS is not just a rigid structure, but it continuously adapts to its surrounding environment.…”

Section: Discussionmentioning

confidence: 99%

Mature dentate granule cells show different intrinsic properties depending on the behavioral context of their activation

Peret

Pléau

Pearlstein

et al. 2018

Preprint

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1The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a 2 small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the 3 large majority remains silent. To date, the properties of this active subset of neurons remain 4 61 5 throughout the experiment (see Materials and Methods), received a water reward at the end of 62 the track after successfully traversing the full track length. After receiving a reward at the first 63 reward zone, the mice then turned around for running in the opposite direction to receive the 64 next reward at the end of the track. In the first sessions (up to 8), the mice moved slowly and 65 erratically along the track as they learned the task. By 8-10 sessions, the mice moved 66 consistently back and forth along the track, and they received rewards at increasing rates over 67 time (1.14 ± 0.05 reward/min, n = 8 mice), they ran reliably back and forth along the track, and 68 they slowed down before reaching the track end consistent with learning of the task (Figure 69 1C). 70To analyse the fraction of DGCs activated in the different behavioral contexts (see above), we 71 used a strain of transgenic mice in which the synthesis of fosGFP fusion protein is controlled 72 by the promoter of the activity-dependent immediate early gene (IEG) c-fos (see Materials and 73 Methods). These mice enabled an ex vivo characterization of activated cells with a recent history 74 of elevated activity in vivo (Barth et al., 2004; Yassin et al., 2010) . In VR training conditions, 75 examination of cells expressing fosGFP was performed ex vivo in hippocampal slices obtained 76 shortly after the last training session (about 18-20 sessions, see Materials and Methods).77Quantification of cells expressing fosGFP was performed in the dorsal hippocampus, which is 78 known to play a crucial role in spatial memory (Moser et al., 1993). When mice were 79 maintained in their home cage, a discreet fraction of DGCs (Prox1-positive, Figure 2C) was 80 activated, since they expressed fosGFP (fosGFP + cells) (1.06 ± 0.1% of DGCs, n = 25 slices, n 81 = 6 mice) (see Figure 1D,E, Materials and Methods) . In line with previous observations (Liu 82 et al., 2012; Kirschen et al., 2017; Shevtsova et al., 2017; Stefanelli et al., 2016), we observed 83 a significant higher fraction of fosGFP + cells in the dorsal hippocampus in mice trained in VR 84(1.92 ± 0.16% of DGCs, n = 19 slices, n = 5 mice, p< 0.0001) ( Figure 1D, E). 85 6 We then explored the distribution of fosGFP + cells across the DG in dorsal hippocampus in the 86 different experimental conditions. To address this question, we plotted the localization of 87 fosGFP + cells in DG and investigated their lateral and radial distributions. DG cell layer extends 88 laterally from the upper (suprapyramidal) blade to the lower (infrapyramidal) blade and from 89 the outer layer (near the molecular layer) to the inner layer (near the hilus) in a radial direction 90 (Altman and Bayer , 1990). In order to reliably...

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Plasticity of the Axon Initial Segment: Fast and Slow Processes with Multiple Functional Roles

Cited by 31 publications

References 83 publications

Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats

Mature dentate granule cells show different intrinsic properties depending on the behavioral context of their activation

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