Opioid receptor distribution in the claustrum-dorsal endopiriform complex
Bibliographic record
Abstract
Abstract The claustrum and dorsal endopiriform regions form a thin subcortical sheet reciprocally connected to the neocortex that is enriched in opioid receptors. The precise cellular distribution of opioid receptors within this region remains unclear. Using multiplexed fluorescence in situ hybridization (mFISH) and hierarchical cluster analysis, we mapped the expression of mu ( Oprm ), delta ( Oprd ), kappa ( Oprk ), and ORL1 ( Oprl ) opioid receptor genes at single-cell resolution in the mouse claustrum-dorsal endopiriform. Among 2,269 neurons analyzed, six transcriptional clusters were identified: three excitatory (CLA, CLA/OPRK, cortical excitatory) and three inhibitory (SST, PVALB, broad inhibitory). Oprk expression was uniquely restricted to excitatory claustrum neurons and particularly enriched in the CLA/OPRK cluster which was comprised largely of Synpr + claustrum core projection cells. In contrast, Oprd, Oprm , and Oprl genes were more broadly distributed across both excitatory and inhibitory populations, with Oprd enriched in parvalbumin ( Pvalb) inhibitory neurons and Oprl in somatostatin ( Sst) inhibitory neurons. Spatial mapping confirmed that Oprk expressing cells were concentrated within the claustrum core, whereas other receptor subtypes extended across the entire claustrum and into adjacent cortical regions. A comparable distribution of opioid receptors was observed in the neighbouring dorsal endopiriform. Analysis of a publicly available single cell sequencing dataset of the macaque claustrum also revealed a similar receptor distribution, where Oprk expression was enriched within a subset of excitatory projection neurons, and Oprm,Oprd , and Oprl expressed widely in both inhibitory and excitatory cells. Together, these findings demonstrate an evolutionarily conserved, cell-type-specific organization of opioid receptor expression in the claustrum-dorsal endopiriform. These results indicate that kappa opioid receptor expression is a defining molecular feature of excitatory claustrum projection neurons and suggest distinct roles for other opioid receptors in modulating inhibitory and cortical circuits.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".