Hey, Calcium, show me the way!
Most (if not all) questions about neuroscience can be answered with <blah blah blah> Calcium (or so it was rumoured at the Neural Systems and Behaviour Course in the MBL back in the ‘90s). Humour aside, there is some truth to the statement, and Sheng Wang, Luis Polo-Parada and Lynn Landmesser examined the role of calcium changes in developing motoneurons.
Their work looked at how calcium changes may be associated with the process through which neurons in the spinal cord find their target muscles, and they did so in a well known system, one that Lynn Landmesser has dedicated most of her career to. The neurons in the spinal cord at the lumbosacral level are organized in longitudinal columns that span several vertebral segments. Neurons in each column will connect with a very specific leg muscle. This means that neurons at different spinal levels, but innervating the same muscle, will have their axons come out through different spinal nerves. All of the axons from different nerves come together at the plexus at the base of the limb where they sort out; axons that will connect with the same muscle become clustered. This has become a wonderful system in which to study how neurons know ‘who’s who’, and make sure they just ‘stick with their own kind’, an important process that avoids incorrect innervation patterns during development.
Also during development, the motoneurons become electrically active, producing burst of rhythmic electrical activity. The patterns of activity are characteristic of each motoneuron pool (that is, the group of motoneurons innervating an individual muscle), and changing the normal rhythm produces errors in axon guidance. Because calcium is known to be involved in many cellular responses, and because electrical activity can increase the levels of calcium inside the cell, the group looked at how calcium in the cell was changing during the bursts of electrical activity.
They found that the electrical rhythmic activity produced calcium transients in early developing motoneurons, even in some that were still migrating towards their final position in the spinal cord. All motoneurons were initially quite synchronous with respect to the calcium changes, but the duration of the calcium transients was different in different motoneuron pools. These differences in duration in the calcium transient could contribute to the downstream signaling that leads to the identity-specific behavior of the axons in the periphery.
One interesting finding is that blocking non alpha-7 nicotinic receptors blocked the spontaneous bursting but did not prevent calcium transients from happening under electrical stimulation. Further, although these channels underlie the bursting activity under normal conditions, the calcium transients were able to propagate across motoneurons while the channels were still blocked. This suggests that although these receptors may normally be involved in the production of electrical bursts, other neurotransmitter systems may be able to operate to allow the propagation of calcium transients.
As the authors suggest, the next step will be to see whether the difference in the duration of calcium transients in different motoneuron pools are sufficient to produce the phenotypic differences that provide each motoneuron with its ability to recognize its ‘own kind’ and find their way to the correct target.
Wang, S., Polo-Parada, L., & Landmesser, L. (2009). Characterization of Rhythmic Ca2+ Transients in Early Embryonic Chick Motoneurons: Ca2+ Sources and Effects of Altered Activation of Transmitter Receptors Journal of Neuroscience, 29 (48), 15232-15244 DOI: 10.1523/JNEUROSCI.3809-09.2009
Disclaimer: Lynn Landmesser was my PhD supervisor.