Npsr1

Neuropeptide S receptor (G protein-coupled receptor 154) (G protein-coupled receptor PGR14)

Spatial tier: RESTRICTED · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 17/554

44.6Discovery Score

41.8Targetability Score

CEvidence grade C

What this means: Npsr1: fine CCF profile is restricted toward SCO (top regions: SCO, AV, STN, AIp6b, PDTg; 17 positive regions); direct spatial validation is still required.

Function in SCO: evidence, prediction, innovation

Gene function

Npsr1 encodes the neuropeptide S receptor (GPR154), a class A GPCR coupling to Gs and Gq for the 20-amino-acid peptide neuropeptide S, which is made by a small pontine cell group near the locus coeruleus. NPS-NPSR1 signalling has the unusual combination of increasing arousal and wakefulness while reducing anxiety; human NPSR1 variants are associated with asthma and with anxiety phenotypes.

Region function

The subcommissural organ is a tiny ependymal secretory gland at the entrance of the cerebral aqueduct beneath the posterior commissure; it releases SCO-spondin into the CSF, where it condenses into Reissner's fibre, and its failure causes aqueductal stenosis and hydrocephalus.

Published in this region

inferred No region-specific literature found. Rodent NPSR1 mRNA and binding are concentrated in amygdala, midline thalamus, hypothalamus and cortex, and the established Npsr1 phenotypes are behavioural: knockout mice show altered anxiety and arousal responses (Duangdao 2009), NPS is anxiolytic and arousing in mice (Leonard 2008), and a knock-in of the human rs324981 variant changes emotionality and cognitive flexibility (Rappeneau 2025).

Predicted function

Prediction: a genuine SCO signal would be unusual and, if confirmed, would most plausibly link arousal state to CSF secretion: Gs/Gq activation of SCO ependymocytes would raise cAMP and calcium and stimulate SCO-spondin release, coupling wakefulness to CSF composition and flow. The test is intracerebroventricular NPS with SCO-spondin and Reissner's-fibre readouts rather than behaviour, since an SCO-restricted Npsr1 deletion is not predicted to change anxiety or arousal. Note that the midbrain SCO region borders periaqueductal tissue where NPSR1 expression is better supported.

Innovation

★★★☆☆ 3/5 NPSR1 itself is well studied behaviourally, so novelty here rests entirely on an SCO localisation that still needs validating.

Tools

Npsr1 knockout mice (Duangdao 2009) and the rs324981 knock-in line (Rappeneau 2025); NPS peptide agonist; antagonists SHA 68 and the naphthopyranopyrimidine series; anti-NPSR1 antibodies; FoxJ1-CreER for ependymal targeting; no Npsr1-Cre in common use.

References

Direct evidence located at the region

Npsr1 Allen ISH at the CCF centroid of SCO

Allen ISH experiment 70560288, section image 70390582 (section 230): the section that contains the CCF centroid of Subcommissural organ according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Look it up yourself: Allen Mouse Brain ISH for Npsr1 Allen reference atlas: SCO (structure 599626923)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Npsr1" or by parcellation_substructure "SCO")All genes confined to SCO + 3-D brain

Direct spatial evidence

SCO MERFISH region locator — Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

SCO

3.93

3.86

STN

AIp6b

1.77

PDTg

1.63

PMv

1.59

CLA

1.54

EPd

1.4

DMH

1.39

AIp6a

1.34

SPFm

1.32

ORBvl5

1.29

POST

1.24

PSTN

1.23

SPFp

1.2

BLAa

1.17

PRE

1.12

MPT

1.05

AIv6a

1.04

SLD

0.996

Evidence and specificity

Evidence status: PREDICTED_FINE
Direct sources: None; predicted localization only
Exclusive threshold: 12 positive regions out of 554
Spatial specificity: 0.317
Top-region fraction: 0.076
Filter status: PASS

Interpretation limits

Cell-type-to-region projection is imputed expression, not direct spatial measurement.
Adult reference atlases do not establish stability across age, sex, strain, state, or disease.
Transcript abundance does not guarantee protein abundance or genetic-tool performance.