A conserved population of genetically defined striatal neurons gates opioid reward
Drake, O. R.; Fiore, C. M.; Jorgensen, E. T.; Newman, C. E.; Potter, L. A.; Trull, A.; Pradeep, A.; Ianov, L.; Peters, J.; Heinsbroek, J. A.; Day, J. J.
Show abstract
A longstanding paradox in striatal circuit architecture is that opioid reward depends on -opioid receptors ({micro}ORs) in nucleus accumbens medium spiny neurons (MSNs), yet {micro}OR function is not explained by the canonical D1/direct and D2/indirect pathway organization. Here, we identify a rare MSN population marked by Chst9 that exhibits exceptionally high expression of the {micro}OR and is conserved across species. Notably, Chst9-MSNs comprise a specialized indirect pathway striatal neuron subtype that is molecularly and spatially distinct from canonical striatal populations. Opioids robustly silence Chst9-MSNs, and selective deletion of Oprm1 from this population abolishes fentanyl-conditioned place preference. These findings establish Chst9-MSNs as a critical substrate for opioid reward and define a new cellular framework for therapies targeting opioid use disorder.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A spatial single-cell atlas of the claustro-insular region uncovers key regulators of neuronal identity and excitability 97%
- Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction 97%
- Hyperactivity of indirect pathway-projecting spiny projection neurons drives compulsive behavior 97%
Similar papers in this journal
- Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies 97%
- Netrin-1 regulates the balance of glutamatergic connectivity in the adult ventral tegmental area 97%
- Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function 97%
Similar papers in this journal
Similar papers in this journal
- Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits 97%
- An Amygdalar Oscillator Coordinates Cellular and Behavioral Rhythms 97%
- Projection-Targeted Photopharmacology Reveals Distinct Anxiolytic Roles for Presynaptic mGluR2 in Prefrontal- and Insula-Amygdala Synapses 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.