In control conditions, we observed development of a strong place preference for fentanyl, which is interpreted as rewarding effects. However, in animals that lacked µOR expression in Chst9-MSNs, fentanyl reward was completely lost!

To determine if the µOR expressed by Chst9-MSNs contributes to opioid reward, we developed an AAV-mediated CRISPR-based deletion strategy, resulting in selective loss of µOR in Chst9-MSNs.

Consistent with this, in vivo administration of fentanyl increased levels of phosphorylated pyruvate dehydrogenase (pPDH, a marker of neuronal inhibition) in Chst9-MSNs, but not in nearby Chst9- regions. This agrees with prior literature showing activation of canonical D1-MSNs by opioids.

The µOR is coupled to inhibitory G protein-coupled receptor pathways, leading us to predict that these neurons should be inhibited by opioid agonists. This is exactly what we found - the µOR agonist DAMGO silences Chst9-MSNs and this is reversed by application of naloxone (a µOR antagonist).

Given their high expression of the µ opioid receptor (µOR) in Chst9-MSNs, we suspected a potential role for this population in opioid actions.

Using a cre-dependent viral tracing strategy, we show that Chst9-MSNs surprisingly target the ventral pallidum (outlined here using a substance P stain), and do not project to the midbrain in the same way that classic D1-MSN populations do.

To study this cell population, we generated a transgenic Chst9-Cre-tdTomato rat line, which allowed labeling and genetic access to this population.

Using the 10X Xenium platform for spatial transcriptomics, we identified that Chst9-MSNs occupy unique spatial domains along the boundary of the nucleus accumbens (shown here in magenta).

Notably, Chst9-MSNs show high transcriptional similarity to D1-MSN populations identified in the ventral striatum of other species (including humans), suggesting conservation between species.

Here, we identified and characterized a new ventral striatum MSN subtype, which is marked by the carbohydrate sulfotransferase gene Chst9. Chst9-MSNs exhibit a distinct transcriptional profile from other MSNs, including high expression of the mu opioid receptor gene (Oprm1).

Classically, D1-MSNs form the "direct" pathway out of the striatum, projecting to the midbrain. Conversely, D2-MSNs form an "indirect" pathway that sends projections to the external segment of the globus pallidus and ventral pallidum. www.frontiersin.org/journals/syn...

Congratulations to the 2026 @acnporg.bsky.social travel award recipients! Good to see a lot of familiar names on this list, including @mictott.bsky.social, @jtuscher.bsky.social, @kmcostalab.com, @laurenmac.bsky.social, @chanjenerational.bsky.social, and @outraajeous.bsky.social!

Notice of Award Monday! Grateful to NIDA for supporting some very exciting work defining the cellular and circuit mechanisms that opioids target to produce rewarding effects.

Very cool original artwork by lab MD/PhD student Olivia Drake for Caroline Fiore’s successful master’s thesis defense in the lab. Congratulations Caroline! Much more to come soon on some really important findings that Caroline contributed to.

New preprint led by recent PhD graduate Dalton Fitzgerald characterizing two distinct populations of VTA dopamine neurons that differ in ion channel expression, intrinsic excitability, and response to drugs of abuse. www.biorxiv.org/content/10.6...

Fantastic talk from @christineliu.art as part of the UAB Neuroscience Seminar series - really intriguing to see rigorous quantification of the behavioral effects of psychedelics across several institutions, and mechanistic circuit dissections with cutting edge tools!

The color indices reflect a distinct subclass ID according to the Allen Brain Atlas reference taxonomy. Thanks to the amazing team at @u-bds.bsky.social, which provided all of the analyses to generate these images.

For #FluorescenceFriday, some of my favorite sections from a new 10X Xenium run at different locations in the anterior/posterior axis of the mouse brain (credit to Olivia Drake, an MD/PhD student in the lab). Each dot marks the location of a specific type of deep layer excitatory neuron.

Great conversations with representatives for Senator Britt, Senator Tuberville, Rep. Palmer, and Rep. Sewell as part of @sfn.org's Hill Day activities. We discussed the need for stable and timely federal support for biomedical research and shared what this support means for Alabama. #hillday

Snooping through the lab network drive for #FluorescenceFriday images and came across this stunning image from UAB master's student Caroline Fiore. 🟡 is mu opioid receptor protein in the rat brain in a coronal section that includes the nucleus accumbens and dorsal striatum.

Surprise gift this morning - fresh eggs from @kacummings.bsky.social! The color variation is really neat, apparently this is mainly driven by the genetics of the breed.

Honored to have made the frontal cortex (cingulate?) of @npp-journal.bsky.social reviewers this year!

Now they are trying flattery to make me forget about how slow the NCBI site is...

I am just bummed to see Alabama incorrectly listed second in the alphabetized states list when entering appointments! If you type "AL" it will enter Alaska for you.

The Day Lab will be representing our work at the annual Society for Neuroscience conference (@sfn.org) in San Diego this week in two sessions - stop by to see updates on a lot of really cool science! #SfN2025 #Neuroscience

A final note, buried in a supplemental figure but still very cool. The main place we saw interactions between pain and opioid exposure was in astrocytes as well. Here, pain states often created gene expression changes that were rescued by morphine administration!

Next, we generated an astrocyte-targeted CRISPR tool to allow us to knock down NR3C1 in this population, and found that this also completely blocked the ability of cortisol to induce FKBP5.

Application of cortisol onto these cells robustly increased FKBP5 levels, and this effect could be blocked by pretreatment with the glucocorticoid receptor antagonist mifepristone. We observed no changes when cells were treated with the µOR agonist DAMGO.

To test this directly, we generated a human-derived astrocyte model from cells with a ventral midbrain origin. As you can see here, they are beautiful and express known astrocyte marker genes like GFAP and S100B.

Among the genes that was strongly induced in glial populations was Fkbp5, a co-chaperone closely linked to glucocorticoid signaling and stress response. Transcripts from this gene were increased in astrocytes, microglia, and oligodendrocytes, but not neurons.