Nps

Spatial tier: STRICT_EXCLUSIVE · Class: OTHER · Top region: LC (Locus ceruleus) · Positive regions: 2/554

50.8Discovery Score
43.6Targetability Score
CEvidence grade C
What this means: Nps: predicted fine-region profile is strict-exclusive, with 2 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in LC: evidence, prediction, innovation

Gene function
Nps encodes the precursor of neuropeptide S, a 20-amino-acid peptide named for its N-terminal serine and conserved across tetrapods. It acts on a single Gs/Gq-coupled receptor, NPSR1, raising cAMP and intracellular calcium in target neurons. Centrally administered NPS increases wakefulness while reducing anxiety-like behaviour, an unusual combination of arousal with anxiolysis (Xu et al. 2004).
Region function
The locus ceruleus and the peri-LC shell control arousal and sleep-wake transitions, attention, stress and anxiety, and respiratory/autonomic state through noradrenergic and neighbouring non-noradrenergic populations.
Published in this region
direct NPS-expressing neurons are a TH-negative cluster in the pericoerulear region, medial to the LC core and intermingled with but distinct from Barrington's nucleus CRF neurons; LC noradrenergic neurons themselves lack NPS and NPSR mRNA (Xu et al. 2004; Huang et al. 2022, which also defined the Atoh1-derived, Foxp2-positive parabrachial NPS population). Angelakos et al. 2023 recorded and manipulated Nps-Cre populations and found peri-LC NPS neuron activity tracks vigilance state, but, unlike the parabrachial NPS cluster, their activation did not increase wake or respiratory rate.
Predicted function
Prediction: Peri-LC NPS neurons are positioned to provide local peptidergic feedback onto LC and Barrington's circuits, biasing stress-induced arousal and autonomic output rather than baseline wake. Chemogenetic activation should be mildly anxiolytic and alter stress-evoked LC firing and micturition-related autonomic responses without strong hypnotic/wake effects; Nps deletion or NPSR antagonism with SHA 68 should increase stress-induced anxiety and blunt post-stress arousal recovery.
Innovation
★★☆☆☆ 2/5 The peri-LC NPS cluster has been anatomically and functionally characterized recently, though its behavioural role is still much less resolved than the parabrachial cluster.
Tools
Nps-Cre driver line (used by Angelakos et al. 2023), NPS peptide for ICV/local infusion, NPSR1 antagonist SHA 68, NPSR1 knockout mice, NPS antisera, intersectional targeting with TH-Flp to exclude noradrenergic cells.
References

Direct evidence located at the region

No Allen ISH section could be located at this region's centroid for the recorded experiments.

Direct spatial evidence

MERFISH REGION LOCATOR
LC MERFISH region locator
Real single-cell MERFISH coordinates for the LC (Locus ceruleus) 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

Nps regional expression profile

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

Spatial profile

LC
0.306
B
0.156
SG
0.062
SOCl
0.0461
SOCm
0.0445
NI
0.0411
SLD
0.0365
POR
0.036
Pa5
0.0339
NLL
0.0295
ENTm3
0.0294
RT
0.0282
PCG
0.0267
SUT
0.0257
ENTm5
0.0256
PDTg
0.0238
NTB
0.0238
SPVI
0.0232
PD
0.0227
RPO
0.0225

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.450
Top-region fraction
0.272
Filter status
PASS

Interpretation limits