Matt Banghart

Blood-brain-barrier permeable fluorescent astrocyte probes. https://www.biorxiv.org/content/10.1101/2025.07.10.664185v1

A Chemically Stable Photocaged Noradrenaline Photoactivatable neurotransmitters provide spatiotemporally precise experimenter control over endogenous receptor activation in living tissue. The resulting optical stimulus-neuronal response relationship provides a sensitive assay that can drive quantitative studies into receptor signaling. Here, we report a photocaged derivative of the prominent catecholamine neurotransmitter noradrenaline (NA). Appending a carboxynitroveratryl (CNV) caging group to the 4-hydroxyl of the catechol group produced CNV-NA, which displays good aqueous solubility and chemical stability. We verified CNV-NA’s lack of activity at α1B- and β2-adrenoreceptors expressed in HEK cells using a live-cell cAMP assay. We validated CNV-NA photoactivation at native α2-adrenoreceptors in brain slices of rat locus coeruleus using whole cell electrophysiological recordings. Monitoring the stereotyped outward current response to repeated CNV-NA photoactivation revealed that the neuropeptide substance P suppresses α2-adrenoreceptor signaling in locus coeruleus neurons. This work adds a new reagent to the growing library of photocaged neuroactive ligands, thereby expanding the scope and applications of photopharmacology.

another new reagent from the lab! pubs.acs.org/doi/10.1021/...

Congratulations to the authors, especially Giulia Livrizzi, who conducted the vast majority of this work while a PhD student in the lab.

Understanding the neural basis of placebo will help us develop better therapies for pain and depression. Capitalizing on placebo can reduce our reliance on dangerous drugs, whereas reducing placebo in clinical trials will help reveal the true efficacy of emerging therapies. 9/9

Interestingly, conditioning appears to prime this circuit through a poorly understood process involving peptidergic plasticity. 8/9

Our findings suggest that the vlPAG is a central node in a closed, negative feedback loop through which incoming noxious sensory information is shaped by endogenous opioids to match expectations based on prior experience. 7/9

Using a genetically-encoded opioid sensor developed by @LinTianPhD bit.ly/4i2jHTf, we discovered that the painful test stimulus evokes opioid peptide release in the vlPAG within seconds, but this was only detected after morphine conditioning. 5/9

Using Ca2+ recordings and LOF manipulations, we established an essential role for vlPAG neurons that project to the RVM in both morphine and placebo analgesia. In contrast, we found that cortical input to the vlPAG is only critical for placebo. 4/9

Although we only conditioned the mice to suppress a paw withdrawal (antinociception), the placebo effect extended to unconditioned pain-related behaviors, such as avoidance and escape, indicating that the conditioning protocol produces a general state of analgesia. 3/9

To achieve placebo analgesia in mice, we conditioned them with morphine. This yielded ~50% of the morphine effect on placebo trials! Like most placebo analgesia in humans, the placebo in mice relies on endogenous opioid neuropeptide signaling. 2/9

Top-down control of the descending pain modulatory system drives placebo analgesia In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify the under...

Curious about the placebo effect, especially placebo pain relief? If so, check out our pre-print on placebo analgesia in mice bit.ly/3QlktPq, in which we ask how pain-modulatory neural circuits become activated in the brain to suppress pain in the absence of a drug. 1/9