Wiring a Neural Network

Motivation:

Many forms of brain and spinal cord injuries cut axons, leading to permanent functional deficits. Currently it is not possible to regenerate axons over long distances and accurately reconnect them with the appropriate target. Our lab has developed a micromanipulation technique to initiate, elongate and functionally connect new branches at remarkable speeds, enabling the (re)wiring of neuronal networks. This technique opens the possibility of creating neuronal circuits in vitro, and allows:


  • The study of signal propagation models and transfer functions of any neuronal network.
  • Recreating the connectome from in-vitro neurons.
  • Microneurosurgery for neuronal regeneration.
  • The implementation of brain machine interfaces.


Electrically Functional Artificial Connections:


Functional presynapses are formed when in contact with a PDL coated bead for longer than 30 minutes (top-left image). These beads can be micromanipulated at remarkable speeds (60 times faster than natural growth) into contact with dendrites from another neuron (top-right image). Here, we show that this connection is electrically functional 24 hours later by stimulating an action potential in the presynaptic neuron and recording an action potential in the postsynaptic neuron (bottom figure).




M.H. Magdesian, M. Lopez, M. Mori, D. Boudreau, D. Oliver, A. Goulet-Hanssens, D. Gobert, W. Paul, X.Y. Xua, R. Sanz, Y. Miyahara, J.-F. Desjardins, C.J. Barrett, E. Ruthazer, A. Fournier, Y. De Koninck, and P. Grutter 
J. Neuroscience, 3, 979-987 (2016)

Magdesian, M. H., Anthonisen, M., Lopez-Ayon, G. M., Chua, X. Y., Rigby, M., Grütter, P. 
J. Vis. Exp. (124), e55697, doi:10.3791/55697 (2017).

Remarkably Fast Extension Speeds:

Using the above micromanipulation technique, we can pull at a remarkably fast 0.5um/s (about 60 times faster than regular growth) to wire any two neurons together. The neurite contains actin, tubulin and neurofilament as in a regular axon. Current research questions are:

  • Why are we able to pull so fast? 
  • Is the neurite actually growing at this speed or is the scaffolding pulled out and the cytoskeleton fills in afterwards? 
  • How far can be pull?
  • What are the mechanical properties of the neurite?
  • Where does all the additional material come from?
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