DREADD-induced presynaptic silencing

This is something I've been hearing about for some time and is now on-line in Neuron from Stachniac, Ghosh and Sternson wherein they nicely demonstrate that hM4Di induces presynaptic silencing (via an unknown but likely interesting mechanism).

They also report an hM4D-neurexin variant which targets to axons.  We also have such a beast which may have improved surface expression and transport which may be similarly useful and is now available to all who wish to use it.  I see the Sternson variant is now available via ADDGENE.

This will be a highly useful reagent for spatio-temporal control of synaptic transmission. I note that Steve Mahler from Gary Aston-Jones' lab has also reported in Nature Neuroscience what appears to be a similar observation related to presynaptic dopamine release via local infusion of CNO.

Comments

  1. Hello, I was wondering if the expression of DREADDs is the same for the whole neuron, i mean it is expressed in the cell bodies and axon terminals in the same way?

    Thanks!

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    1. Although we haven't studied this in great detail if you examine two of our papers it appears hM3D has some preference for somatodendritic targeting (though it appears in axons as well) while hM4D has some axonal preference.

      Refs: Neuron. 2009 Jul 16;63(1):27-39 for hM3D
      Neuropsychopharmacology. 2014 Jul;39(8):1880-92. for hM4D

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