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Updated: Jun 16, 2026

A Method for Remotely Silencing Neural Activity in Rodents During Discrete Phases of Learning
Published on: June 22, 2015
Silencing neurotransmission with membrane-tethered toxins
Sebastian Auer1, Annika S Stürzebecher, René Jüttner
1Molecular Neurobiology group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Abstract:
At synaptic terminals, high voltage-activated Ca(v)2.1 and Ca(v)2.2 calcium channels have an essential and joint role in coupling the presynaptic action potential to neurotransmitter release. Here we show that membrane-tethered toxins allowed cell-autonomous blockade of each channel individually or simultaneously in mouse neurons in vivo. We report optimized constitutive, inducible and Cre recombinase-dependent lentiviral vectors encoding fluorescent recombinant toxins, and we also validated the toxin-based strategy in a transgenic mouse model. Toxins delivered by lentiviral vectors selectively inhibited the dopaminergic nigrostriatal pathway, and transgenic mice with targeted expression in nociceptive peripheral neurons displayed long-lasting suppression of chronic pain. Optimized tethered toxins are tools for cell-specific and temporal manipulation of ion channel-mediated activities in vivo, including blockade of neurotransmitter release.
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