G12/13 PREFERRING DREADD
In a recent Cell paper the authors provide an elegant approach to create a G12/13-preferring DREADD. This will have a huge impact!
Posts
Dissolving Salvinorin B for KORD experiments
From Krashes lab: We make SalB fresh the day of injection. We use pure DMSO to dissolve SalB at a 10mg/kg concentration. For a 30g mouse: 30uL of a 10ug/uLsolution It's a very small volume, we usually do SC injection
DREADDs cure cancer?
An interesting and provocative paper recently published in Nature Communications: " Modulation of anti-tumor immunity by the brain’s reward system " They conclude: " Activation of the reward system in tumor-bearing mice (Lewis lung carcinoma (LLC) and B16 melanoma) using chemogenetics (DREADDs), resulted in reduced tumor weight. This effect was mediated via the sympathetic nervous system (SNS), manifested by an attenuated noradrenergic input to a major immunological site, the bone marrow. Myeloid derived suppressor cells (MDSCs), which develop in the bone marrow, became less immunosuppressive following reward system activation. By depleting or adoptively transferring the MDSCs, we demonstrated that these cells are both necessary and sufficient to mediate reward system effects on tumor growth. Given the central role of the reward system in positive emotions, these findings introduce a physiological mechanism whereby the patient’s psychological state can impact anti-...
Chemogenetics to identify the "specific contributions of individual areas and the circuit mechanisms through which they interact to modulate learning"
Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity Using viral tracing and pharmacogenetic techniques, we show that prelimbic (PreL) and infralimbic cortex (IL) exhibit reciprocal PreL↔IL layer 5/6 connectivity. In set-shifting tasks and in fear/extinction learning, activity in PreL is required during new learning to apply previously learned associations, whereas activity in IL is required to learn associations alternative to previous ones. IL→PreL connectivity is specifically required during IL-dependent learning, whereas reciprocal PreL↔IL connectivity is required during a time window of 12–14 h after association learning, to set up the role of IL in subsequent learning. Our results define specific and opposing roles of PreL and IL to together flexibly support new learning, and provide circuit evidence that IL-mediated learning of alternative associations depends on direct reciprocal PreL↔IL connectivi...
Acoustically taregeting DREADDs
This is a pretty amazing paper which can be found here: The basic approach is outlined above and seems to work amazingly well in mice. Great to see if this can be translated to larger brains.
New chemogenetic toolkit for G-protein vs arrestin signal activation
Our new paper is now out in BioarchivX and can be found here. A Chemogenetic Platform for Spatio-temporal Control of β-arrestin Translocation and Signaling at G protein-Coupled Receptors
SCIENCE: DREADDs and Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis
Interesting first-release Science paper here with direct CNO injections
Great use of multiplexing KORD, hM3Dq and hM4Di to interrogate histaminergic control of grooming
paper here in PNAS Cool videos as well here:
DREADDs: Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus
Thalamic neuronal activity was modulated after injecting an adeno-associated virus (AAV) expressing an engineered acetylcholine Gi-protein coupled receptor. This receptor inhibits neuronal firing when bound by clozapine -n- oxide (CNO). VGAT expression was attenuated in the thalamus by injecting an AAV construct that expressed a VGAT silencing shRNA. VZV induced nociception was significantly decreased after administering CNO in male rats. Nociception significantly increased concomitant with increased thalamic c-fos expression after attenuating thalamic VGAT expression. These data establish that the lateral thalamus (posterior, ventral posteromedial , ventral posterolateral and/or reticular thalamic nucleus) controls VZV induced nociception in the orofacial region, and that GABA in this region appears to reduce the response to VZV induced nociception possibly by gating facial pain Nice controls here: ...
Galanin-expressing GABA neurons in the lateral hypothalamus modulate food reward and non-compulsive locomotion
Really great set of controls here
CNO via minipump (Science paper, Moser labs)
I often get questions regarding CNO via minipump and here is a nice example where that seems to work.
DREADDs and OPTO modulating VTA terminals
Dopamine terminals from the ventral tegmental area gate intrinsic inhibition in the prefrontal cortex
DREADD-modulation of 5HT neurons causes perseverative responding
Activity patterns of serotonin neurons underlying cognitive flexibility
Nice use of DREADDs to dissect GPCR signaling underlying anxiety
Great bit of work by Kash lab and many others using Gi, Gs and Gq =DREADDs to deconstruct pathways essential for anxiety in BNST
