,
15 tweets,
4 min read
Read on Twitter
Hmm... Spatiotemporal ontogeny of brain wiring advances.sciencemag.org/content/5/6/ea… I guess all those people working on axon guidance can go home now...
This is nice modeling work, by @AlGoulas @richardfbetzel + Claus Hilgetag and I have no doubt that spatial proximity + relative maturation timing play crucial roles in determining patterns of brain connectivity...
But just because it can be modeled that way, with a few simple parameters, does not mean it actually works that way. Neurons don't in fact just project any old way and connect with whoever is around...
They make extremely stereotyped projections, oriented from the outset to specific directions, bypass all kinds of inappropriate targets and eventually find their predestined partners
And we know that those projection and connectivity decisions are encoded in the genome and mediated by guidance molecules because these can be mutated to alter connectivity
Clearly there are some larger organisation principles at play as well, and this paper nicely elucidates some of them. (And these may be especially important in development of the cerebral cortex)...
But the field has visited this theoretical terrain before - a few simple principles simply won't get you the real complexity of brain circuitry.
What would be interesting would be to think of ways to experimentally manipulate proximity and timing and predict what would happen to connectivity...
This can be done indirectly, as in this work from my own lab, for example, in collaboration with @GLB_Lab and @ZoltanMolnar64... Specificity and Plasticity of Thalamocortical Connections in Sema6A Mutant Mice dx.plos.org/10.1371/journa…
When the Sema6A guidance molecule is mutated, axons from the visual thalamus, that should project specifically to the visual cortex (via a long and highly specified pathway) get misrouted and instead project to the amygdala...
This leaves what should be visual cortex initially uninnervated and that territory gets invaded by axons from neighboring somatosensory thalamus. (visualised here by back-labeling...) 
So far, this might seem to support the proximity and timing hypothesis - that neurons will innervate whoever is nearby and ready...
But what happens next demonstrates instead the tremendous specificity of the connectivity program...
Visual thalamic axons that initially project into the amygdala continue along a completely different route on the outside of the cortex, to arrive (at least four days late) to visual cortex, evict the interloping SS axons and establish almost normal innervation of V1
In this instance at least (and there are many such examples in the literature) altering the spatiotemporal relationships is not sufficient to override the information encoded by connectivity molecules
