How do neurons find each other?

Question

Neurons form complicated networks in brains, but their connections can't be random (at least not entirely). Brains function similarly among all members of individual species, and that functionality is largely dependent on neuron organization. Furthermore, various brain regions have predictable functions, and there are even parts of the brain where specific cells carry out specialized functions (place cells are an interesting example).

Great! We know neurons can organize into very complex networks, but how? They need to find each other, somehow.

The best I can guess is that either:

• Neurons find other target neurons with specific chemical signals.
• Neurons don't "find" each other, exactly, but grow in predetermined shapes from from set locations. In this case, the connections would simply be due to neurons bumping into each other as they grow in their predetermined paths.
• Or both.

In the first case, there would be a mechanism for searching each other out. In the second, there would be a mechanism for staying in one spot (and growing from there). What are the names of said mechanisms? How do I find out more about them?

Answer 1

Q: We know neurons can organize into very complex networks, but how?

The answer is your first guess: Neurons find other target neurons with specific chemical signals.

Q: What are the names of said mechanisms?

This process is called axon guidance, by which the growth cones of developing axons are directed to reach their targets. This process depends upon a slew of cellular and molecular cues. The first axons to grow in any particular brain region are called pioneer axons and are the most dependent upon these cues. Later axons are able to follow (and diverge from) previous axons by the interaction of cell adhesion molecules on their surfaces. Dendritic development is also important for your question, but dendrites tend not to travel as far.

Here are some of the molecules that we know to participate in axon guidance:

• Cell adhesion molecules and substrate adhesion molecules, including IgSF CAMs and cadherins
• Some chemokines, e.g. CXCL12
• Netrins, ephrins, and semaphorins
• Slits, via the Slit-Robo cell signaling pathway
• Developmental morphogens, e.g. Wnts and Hedgehog

The list goes on, and this is an area of active research. Each of these cues is recognized by one or more specific receptors on the developing neuron, which upon recognition of the ligand molecule either attracts or repels the axon from (or both, depending on the context). Recognition can function either short-range (by direct contact with a ligand) or long-range (e.g. by detection of a concentration gradient), depending on the molecular cue.

For more information, you may want to read Sanes et al., Development of the Nervous System.

Answer 2

This is a very good question.

There are specific chemical signals, for instance:

1.) LRR proteins, which help signal neurons to each other. These are transmembrane proteins which are characterised by their leucine-rich repeat. They serve as some kind of protein labels for other neurons. These proteins are also known in pathogen recognition in our immune system.

2.) We also have Neurexins. This is a presynaptic protein that helps connect neurons in the synapse. They are known binding a family of proteins, the Neuroligins. Neurexins have actually also previously been implicated in autism/shizophrenia. The failure of the right connections likely lead to an incorrect balance of excitatory and inhibitory connections, which result in dysfunctions in neural circuits and consequently to such maladies.

https://en.wikipedia.org/wiki/Neurexin (wikipedia)

http://www.ncbi.nlm.nih.gov/pubmed/23931994 (research)

(http://) books.google.nl/books?id=qMe5BgAAQBAJ&pg=PA152&lpg=PA152&dq=neurons+predetermined+paths&source=bl&ots=LsYBkr431V&sig=ewc2geKBL1QUYogPXPh21tGC5Ww&hl=nl&sa=X&ved=0ahUKEwiTqJ3Z-YHOAhWLVxQKHcN2DI84ChDoAQgrMAI#v=onepage&q=neurons%20predetermined%20paths&f=false (book)

(http://) www.ncbi.nlm.nih.gov/pubmed/17868438 (research)

These sites could help out in further research (apparently I cant post more than 2).

There are probably many more proteins involved, but these are the main ones I know of, and the ones I have studied in my education. Scientists also often state that there is no predetermined path, but rather a rearrangement of neural pathways (I´d suggest visiting the third website link, philosophy of psychology page 152).

I hope this helped you out with your question, and if you've got more questions on how these molecules work with signaling in depth, I´d be glad to answer them.