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-tumor immu…

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


Great use of multiplexing KORD, hM3Dq and hM4Di to interrogate histaminergic control of grooming


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 acetylcholineGi-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 posteromedialventral 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