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 connectivity.

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