Gross, G.G., Straub, C., Perez-Sanchez, J., Dempsey, W.P., Junge, J.A., Roberts, R.W., Trinh, l.e. .A., Fraser, S.E., De Koninck, Y., De Koninck, P., Sabatini, B.L., Arnold, D.B. (2016) An E3-ligase-based method for ablating inhibitory synapses. Nature Methods. 13:673-8.
Although neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells.