How does an axon "know" it's not connecting to its own neuron?

Question

I recently read about an experiment where they removed the dendrites and axons from rat neurons and placed them on a grid. After a while they started reconnecting and were able to learn things.

Since I'm trying to create a model simulating this, I'd like to know (as much as is needed to make it look at least a little bit realistic) how they reconnected. As far as I know some molecules are secreted attracting or repelling axon growth cones.

I think I can model that part, but the problem is that the axons can easily grow back to where they came from, so how do the axons in a brain 'know' they are not growing back to the neuron they originated from.

Answer 1

I think I can partially answer you question. As far as I'm aware, there are many surface receptor molecules such as ephrins that are responsible for axonal guidance and dendritic repulsion in developing organisms such as flies (Drosophila). As you can tell this is extremely crucial since its important for neurons to spread their dendrites and axons as far as possible, evenly spaced out with axons bifurcating (separating) correctly and not sticking together. This is for example important in the Drosophila brain for axonal projections into different lobes.

One such surface receptor, which helps achieving the above is Dscam (Down syndrome cell adhesion molecule) (schmucker et al 2000 Cell). Dscam gene is expressed in over 38000 isoforms (through complex alternative splicing of Dscam mRNA) in flies. It is the homophilic binding and subsequent repulsion of Dscam protein isoforms that enables an intrinsic self-recognition for repulsion of same-cell axon. As far as I understand it, if a number of similar Dscam isoforms are present on axons or dendrites of a neuron, this is self recognised and the dendrites and axons get repelled from one another. This is the molecular pathway that ensures sister dendrites are not adhered together or become concentrated in one area.

In the absence of Dscam or when Dscam protein isoform diversity is removed flies die during larval stages and the early embryonic axonal patterning of the fly nervous system is clearly disrupted. In the absence of Dscam protein, Bolwig's axons exhibit frequent axon pathfinding errors at a specific intermediate target. Most of these processes are conserved in mammals.

For further information please look at Schmucker & chen, 2009 Genes and Dev

Answer 2

In cases of severe head injury where a large portion of neurons and their connections get shredded. I don't think a neuron would be very choosy when presented with quite a few axons and lots of intracellular fluid

There are coup and the contra coup (p silent) brain injuries that occur because the brain bounces back and forth in the skull. The contra coup, other side contusion (bruise) is usually worse. A lot of axonal injury occurs in the brain stem and since the basics of life (breathing centers) a severe injury to the brain stem can cause not surviving the injury.

Probably speed of healing I is the priority. I forgot which journal it was in but those with a college education were 60% more likely to have a good recovery while those with just a high school diploma have only 10-20% chance of having a good recovery. It's a similar ranking when it comes to neuronal connections.

Thank you for answering my curiosities on how indeed does one heal from Diffuse Axonal Injury (DAI) on a molecular basis. I was a 1sr yr. radiology resident when I had a severe TBI or Traumatic Brain Injury. TBI is the fancy way of saying brain damaged. But now we know victims of severe head injury can recover and even grow new neurons until old age.