Chst9 marks a spatially and transcriptionally unique population of Oprm1-expressing neurons in the nucleus accumbens

Andraka, Emma; Phillips, Robert A.; Brida, Kasey L.; Day, Jeremy J.

doi:10.1016/j.addicn.2024.100153

Cited by 4 publications

(1 citation statement)

References 58 publications

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“…smFISH was performed (#323136, ACD Bio, Newark, CA, USA) to probe for Reln, Drd1 and Fos ( Fos quantification) or Reln, Drd1 , and Drd2 ( Reln characterization) or Reln, mCherry , and dCas9 ( Reln knockdown) following manufacturer’s protocol for fresh-frozen tissue, as previously described 111 112 . Briefly, tissue was submerged in ice-cold 10% normal-buffered formalin for 15 minutes and then serially dehydrated with ethanol, then treated with hydrogen peroxide, followed by protease IV digestion.…”

Section: Methodsmentioning

confidence: 99%

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

Brida,

Jorgensen,

Phillips

et al. 2024

Preprint

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SummaryDrugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by theRelngene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early geneFosinReln+neurons after cocaine experience, and also revealed enrichment ofRelnmRNA inDrd1+ medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selectiveRelnknockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss ofRelnprevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.

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Section: Methodsmentioning

confidence: 99%

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

Brida,

Jorgensen,

Phillips

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior

Fitzgerald,

Day

2025

Addiction Neuroscience

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Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution

Yang,

Fang,

Lynch

et al. 2024

Preprint

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The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used snRNA-seq and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding the structure and function of the VP and identified key neuropeptides, neurotransmitters, and neuro receptors that could be targeted within specific VP cell types for functional investigations.

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Chst9 marks a spatially and transcriptionally unique population of Oprm1-expressing neurons in the nucleus accumbens

Cited by 4 publications

References 58 publications

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward

Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior

Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution

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