science
Researchers Engineer Fish Proteins to Create Electrical Synapses in Mammalian Brain Circuits
A research paper published by Nature describes the development of an engineered electrical synapse using two connexin proteins from white perch fish. The proteins were modified to form synapses selectively with each other but not with mammalian connexins. The approach, called LinCx, was tested in worms and mice to strengthen communication between distinct cell types and alter behavior.
May 14, 1:46 PM·2m read2 sources
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Electrical signalling between different populations of brain cells supports cognitive and emotional functions. Approaches that can selectively regulate signalling between specific cell types in mammalian neural circuits have been limited. A research paper published by Nature reported the engineering of an electrical synapse using two connexin proteins from white perch fish.
The proteins, connexin 34.7 and connexin 35, were modified through protein mutagenesis. Researchers developed a new in vitro system to test connexin hemichannel docking and used computational modelling to identify a structural motif involved in electrical synapse formation.
Targeting this motif produced hemichannels that dock with each other to form functional electrical synapses but do not interact with major connexins found in the mammalian central nervous system. The engineered synapse was validated in vivo in Caenorhabditis elegans worms and Mus musculus mice.
It strengthened communication across neural circuits made up of distinct cell types and modified the animals' behaviour. The paper establishes a method called long-term integration of circuits using connexins, or LinCx, for precision circuit editing in mammals.
By exploiting protein mutagenesis and computational modelling, the team identified a structural motif contributing to electrical synapse formation. The modified connexin 34.7 and connexin 35 hemichannels were designed to interact only with each other.
This selectivity avoids unintended coupling with the mammalian connexins normally expressed in the central nervous system. The new in vitro assay system allowed direct testing of hemichannel docking. Computational modelling supported the identification of the key motif.
