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. UnknownJanuary 2, 2015 at 9:14 PM

    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!

    ReplyDelete
    Replies
    1. zendudestJanuary 3, 2015 at 7:01 AM

      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

      Delete

Post a Comment

Popular posts from this blog

CNO in drinking water

We frequently get requests regarding protocols for putting CNO in the drinking water for long-term studies. Here is our protocol: 1. Dissolve the CNO in a small volume of DMSO 2. Diluted the dissolved CNO in drinking water (e.g., 5mg/200ml) 3. Give mice with CNO drinking water  and protect from light using foil-wrapped bottles 4. The mice will receive 5mg/kg/day CNO (assume that mice weight 30g and consume 6ml water per day) 5. Prepare fresh daily. 6. A small amount of saccharine in the drinking water will mask the slightly bitter taste of CNO
Read more

How best to dissolve CNO ...it depends on what it is soluble in (and that depends on the particular polymorph)

I recently received the following question: " My question is with regard to the use of CNO in drinking water (in mouse studies). Your recipe calls for the addition of a small amount of DMSO to dissolve CNO at a concentration of 5 mg in 200 mL. As we and others routinely dissolve CNO in 0.9% saline (no DMSO) at concentrations up to four times this amount, I am curious whether the addition of DMSO to CNO solutions for H2O drinking is critical, or whether the properties of CNO permit it's direct dissolution in H2O at concentrations from 5-20 mg per 200 mL. There appears to be no difficulty dissolving such concentrations in H2O in my hands, but I would prefer to hear your perspective. Is there a published reference for the solubility profile of CNO in H2O or 0.9% saline?" It basically depends upon the source of the CNO.  CNO via the NIH RAID program (which is what we use) is not readily soluble in H20 while commercial CNO is.  Although we've verified that both source
Read more