17.04.2012 17 c.t.
Activity-dependent plasticity at the axon initial segment
by Dr. Matthew Grubb
from MRC Centre for Developmental Neurobiology, King's College London, UK
Ludwig Prandtl lecture hall
Neurons respond to changes in their ongoing electrical activity using a huge variety of mechanisms for plasticity, ranging from molecular alterations through to synaptic modifications and whole-scale morphological remodelling. We recently showed that activity-dependent changes can also take place at a hitherto unappreciated site for plasticity: the axon initial segment, or AIS. This large cellular substructure acts both as a diffusion barrier maintaining axo-dendritic polarity and, because of its large local density of voltage-gated sodium channels, as the site of action potential initiation. In hippocampal neurons subjected to elevated activity conditions, we found that the entire structure of the AIS could move distally along the axon away from the soma (Grubb & Burrone 2010 Nature 465:1070). This activity-dependent relocation reversed upon return to control conditions, and appeared to be triggered by calcium entry through L- and/or T-type voltage-gated calcium channels. It was also associated with an increased current threshold for action potential firing, suggesting that AIS relocation may act homeostatically during development to fine-tune neuronal excitability. My talk will outline these published data on AIS relocation, and will aim to place our results in the context of other recent exciting work in the field. It will also include unpublished ongoing work in my laboratory aimed at elucidating the activity codes and signalling pathways leading to AIS plasticity, and at describing the physiological significance of AIS movement in vitro and in vivo.
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