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Published on: January 12, 2014
Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.
Paola V Plazas1, Xavier Nicol, Nicholas C Spitzer
1Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093, USA. pvplazas@gmail.com
Summary
Electrical activity, specifically calcium (Ca2+) spikes, guides zebrafish motor neuron axons in vivo. This activity-based competition, independent of synaptic transmission, interacts with PlexinA3 signaling for proper axon pathfinding.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Electrical activity's role in axon guidance is well-established in vitro.
- Understanding this role in a developing nervous system in vivo is crucial.
Purpose of the Study:
- To investigate the role of intracellular calcium (Ca2+) activity in zebrafish primary motor neuron (PMN) axon pathfinding in vivo.
- To determine how electrical activity and guidance molecules interact during axon development.
Main Methods:
- In vivo imaging of intracellular Ca2+ in zebrafish PMN during axon pathfinding.
- Perturbation of Ca2+ spiking and overall electrical activity in single PMN.
- Assessment of axon pathfinding errors.
- Analysis of PlexinA3 expression and its interaction with Ca2+ activity.
Main Results:
- PMN exhibit stage-specific Ca2+ spike patterns originating in the distal axon and propagating to the cell body.
- Suppression of Ca2+ spiking in single PMN caused specific pathfinding errors, while silencing all electrical activity did not.
- This activity-based competition was independent of synaptic transmission.
- Combined PlexinA3 knockdown and Ca2+ suppression led to synergistic pathfinding errors, though PlexinA3 transcript levels were not activity-regulated.
Conclusions:
- Spontaneous electrical activity, via Ca2+ spikes, plays a critical role in vivo axon guidance.
- An activity-based competition mechanism regulates axon pathfinding, involving an interaction between electrical activity and the PlexinA3 guidance receptor.
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