Development and Application of Membrane-Tethered Toxins for Genetic Analyses of Neuronal Circuits

Peptide toxins derived from venomous animals are widely employed in neuroscience research because of their ability to manipulate specific ionic currents. However, the detailed characterization of particular classes of ion channels and their contributions to given neuronal circuit is often hampered by the fact that the action of soluble neurotoxins cannot be restricted to single cell populations. Here, we review a recombinant strategy based on genetically encoded membrane-tethered toxins (t-toxins) for long-term inhibition of ion channels and receptors. Due to their membrane attachment, the activity of fused toxins is restricted to the genetically targeted cells, without affecting identical channels on neighboring cells that do not express the t-toxin. This review describes the development and modular design of t-toxins and their application to studies of neurocircuitry using transgenic and viral constructs to target expression to specific CNS cell types in vitro and in vivo.