Rewiring the brain
A technique that gives neuroscientists the ability to edit the connections between neurons has been shown to modify behaviour in nematode worms.
This approach, if translatable to humans, could lead to a new way of understanding how our brains work and even what consciousness is. It may also create a new means of studying abnormal brain connectivity in diseases such as Epilepsy, Alzheimer's and Schizophrenia.
A lot of work has already helped to show how the brain is wired (the human connectome). To find out how that pattern of connections leads to particular behaviours, it is necessary to modify them in precise ways and observe changes in function.
A team of researchers, led by Dr William Schafer from the MRC Laboratory of Molecular Biology in Cambridge (UK), created this tool that enables a change in synaptic connections between the neurons of nematode worms (C. elegans).
The Nematode's Neurons
The nematode worm is an excellent model organism for studying neuroscience. Nematode worms have just 302 neurons, which have all been identified and characterised. Additionally, the roughly 7000 connections between these neurons have all been mapped and widely studied. This simple system allows us to study things in a way that would be very difficult in the neuronal mass of more complex brains like our own.
If we can change specific connections in a small group of neurons it should be easy to discern a functional change and use this information to figure out the typical role.
How the technique works
Neurons, whether they are in nematode worms or humans, communicate via both chemical and electrical synapses. Chemical synapses are a complex mix of lots of proteins that would be difficult to replicate in transgenic models. However, electrical synapses are simple channels, known as gap junctions, that are made of only one type of protein.
The nature of this protein differs between invertebrates and vertebrates. Dr Schafer and his team used this to their advantage by injecting the DNA for vertebrate gap junctions into nematode worm (invertebrate) gonads thus ensuring there wouldn't be any interaction with other neural connections. In the next generations of worms, there were new neural connections made through the expression of these genes; the scientists had created synthetic electrical synapses in an intact nervous system.
They tested the effects of these new connections in two different pairs of neurons. Firstly, they looked at connections formed between two cells that had not previously had any. These neurons are normally used in the worms' response to salt. Usually, salt stimulates increased activity in one neuron and decreased activity in the other. When they were connected with new gap junctions, if one had increased activity then so did the other. This limited their sensitivity to salt.
The other neurons examined are involved in the nematode worms' sense of smell. These neurons are usually joined by inhibitory chemical synapses, but adding electrical synapses caused them to switch to being predominantly excitatory. Therefore, both the pre- and post-synaptic neurons reacted the same way to a stimulus. This abolished the worm's ability to respond to certain smells.
In the future
This technique could be used to study a large range of other neural circuitry. Eventually, by altering synaptic connections we may be able to insert novel behaviours into organisms. Most excitingly, there seems to be no reason why this technique could not be used in vertebrates (i.e. creating transgenic vertebrates expressing innexins to alter neural circuits)
This doesn't only have applications in research. The ability to change these connections could eventually be used in clinical applications. For example, someone suffering from brain damage could have the affected areas bypassed with the creation of new pathways.
Scientifica have helped Dr Schafer to continue with this research by developing a customised sample plate enabling the use of objective lenses with higher magnifications, and have also assisted Dr Shafer with the necessary equipment to carry out electrophysiology on transgenic neurons.
Paper reference
Rabinowitch I, Chatzigeorgiou M, Zhao B, Treinin M, Schafer WR (2014) Rewiring neural circuits by the insertion of ectopic electrical synapses in transgenic C. elegans. Nat Commun. 2014 Jul 16;5:4442. doi: 10.1038/ncomms5442.
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