Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability

By M. Grubb, J. Burrone. Nature, 2010

660 citations recorded by the source corpus.

In neurons, the axon initial segment (AIS) is a specialized region near the start of the axon that is the site of action potential initiation. The precise location of the AIS varies across and within different neuronal types, and has been linked to cells’ information-processing capabilities; however, the factors determining AIS position in individual neurons remain unknown. Here we show that changes in electrical activity can alter the location of the AIS. In dissociated hippocampal cultures, chronic depolarization with high extracellular potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 μm away from the soma of excitatory neurons. This movement reverses when neurons are returned to non-depolarized conditions, and depends on the activation of T- and/or L-type voltage-gated calcium channels. The AIS also moved distally when we combined long-term LED (light-emitting diode) photostimulation with sparse neuronal expression of the light-activated cation channel channelrhodopsin-2; here, burst patterning of activity was successful where regular stimulation at the same frequency failed. Furthermore, changes in AIS position correlate with alterations in current thresholds for action potential spiking. Our results show that neurons can regulate the position of an entire subcellular structure according to their ongoing levels and patterns of electrical activity. This novel form of activity-dependent plasticity may fine-tune neuronal excitability during development.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/25be2d6df3c9830edb12a02dd90f4eede778b3fc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

Citations in the corpus

Mechanisms for Stable, Robust, and Adaptive Development of Orientation Maps in the Primary Visual Cortex (2013, background): “Unlike the linear model units with fixed threshold, real neurons are thought to have intrinsic homeostatic plasticity, whereby each neuron regulates the level of synaptic input required to generate an action potential by changing the number and distribution of its ion channels (Davis and Bezprozvann”
All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins (2014, methodology): “Observation of HPIE in culture 32,33 and in vivo 34 has traditionally required laborious patch-clamp measurements on many cells.”
Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement. (2011, background): “It was recently shown that in addition to changes in inward and outward current densities, enhanced firing (by changes to calcium influx) can regulate the location of the axon initial segment (AIS) so that it moves further from the soma (Grubb & Burrone 2010).”
The Development and Application of Optogenetics (2011, background): “…al. 2005, Gunaydin et al. 2010), lasers (Cardin et al. 2010, Cruikshank et al. 2010, Kravitz et al. 2010, Petreanu et al. 2009), light-emitting diodes (LEDs) (e.g., Adesnik & Scanziani 2010; Grubb & Burrone 2010a,b; Wang et al. 2009), or LED arrays for multisite stimulation (Grossman et al. 2010).”