Like thermostats that switch on heating or cooling to regulate temperature, neurons tune their excitability up or down to weather environmental changes. Who would have thought, though, that nerve cells can do this by deftly repositioning or enlarging their entire axon initial segment (AIS), a specialized spike-initiating region in the cell body? This is what two independent groups report in two Nature papers published online June 13. In the first study, UK scientists found that flooding depolarization into cultured hippocampal neurons shifts the AIS away from the soma, as if this sensitive area backed off from the onslaught. In the second paper, Japanese researchers produce complementary results in studies with live chicks, where deprivation of auditory signal caused the AIS to lengthen in brainstem neurons, as if to catch every dribble of incoming signal. These studies suggest a new form of plasticity that may help neurons calibrate their excitability during development, or as a way of dealing with hearing loss or other sensory deficits.
In the first report, Matthew Grubb and Juan Burrone of King’s College, London, plated out hippocampal neurons from young rats and spiked the medium with potassium to make the cells more depolarized, i.e., more excitable. Immunostaining for voltage-gated Na+ channels and other AIS proteins two weeks later, the researchers saw a dramatic shift in AIS position. “It was quite surprising,” Grubb told ARF. “This whole section of the cell decided to relocate itself away from the cell body.” The AIS moved up to 17 microns down the axon—which might not seem like a lot but is pretty impressive given that cell bodies are typically only ~20 microns wide, Grubb said. “We think this is part of a process called homeostatic plasticity, where neurons can change things about themselves to regulate their activity levels,” he said. It’s as if the neuron sensed it was too active and shifted its sodium channels (the excitable part of the cell) away from the soma to make itself less responsive. “We think this is what the AIS movement might be doing,” Grubb said.
Working independently, researchers at Kyoto University, Japan, used a different system to essentially do the converse experiment. Rather than making neurons more excitable, they decreased activity levels and, as a consequence, saw the AIS nearly double in size. Led by Harunori Ohmori, first author Hiroshi Kuba, and Yuki Oichi removed the cochlea from young chicks and found a week later that this auditory deprivation made the AIS grow to 1.7 times its starting length in brainstem neurons.
The UK researchers also tried depriving their hippocampal neurons of input, but these manipulations “didn’t change anything,” Grubb said. “We’re pretty sure this is because the baseline levels of electrical activity in our cultured neurons are very low, so deprivation isn’t a big alteration for our cells.” Instead, the scientists were able to shift the AIS back to its initial position near the cell body by returning the neurons to control conditions after the two days of blasting depolarization. Though this allowed them to see a reverse-direction AIS shift, it was “still a change in position only,” Grubb noted. “We never saw AIS growth like [the Japanese team].” He said this might be because different types of neurons have different ways of changing their AIS to adapt to input changes.—Esther Landhuis
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- Grubb MS, Burrone J. Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature. 2010 Jun 24;465(7301):1070-4. PubMed.
- Kuba H, Oichi Y, Ohmori H. Presynaptic activity regulates Na(+) channel distribution at the axon initial segment. Nature. 2010 Jun 24;465(7301):1075-8. PubMed.