Nmbr

Neuromedin-B receptor (NMB-R) (Neuromedin-B-preferring bombesin receptor)

Spatial tier: RESTRICTED · Class: GPCR · Top region: PVT (Paraventricular nucleus of the thalamus) · Positive regions: 17/554

45.1Discovery Score
39.9Targetability Score
CEvidence grade C
What this means: Nmbr: fine CCF profile is restricted toward PVT (top regions: PVT, ENTl6a, PERI6a, AON, CM; 17 positive regions); direct spatial validation is still required.

Function in PVT: evidence, prediction, innovation

Gene function
Nmbr encodes the neuromedin B receptor (BB1), one of three mammalian bombesin-family class A GPCRs alongside GRPR (BB2) and BRS3. It couples to Gq, so neuromedin B binding activates phospholipase C, raises intracellular calcium and typically depolarises and excites the target neuron. The system is best known for histaminergic itch transmission, feeding and thermoregulation.
Region function
The paraventricular nucleus of the thalamus is a midline thalamic node for arousal, stress and motivational drive, projecting to nucleus accumbens, amygdala and prefrontal cortex.
Published in this region
expression only Bombesin-like peptide receptor binding sites were mapped across rat brain including midline thalamus by Moody 1988, and Ohki-Hamazaki 1997 cloned mouse Nmbr and described its CNS distribution. The strongest PVT result concerns the sister receptor: Hermes 2013 used perforated-patch recordings to show that gastrin-releasing peptide excites rat PVT neurons through postsynaptic BB2/GRPR by modulating inward-rectifier potassium and a TRPV1-like conductance, establishing bombesin-receptor signalling in PVT but through GRPR rather than NMBR.
Predicted function
Prediction: neuromedin B released in PVT should act as GRP does, using Gq signalling to close inward-rectifier potassium channels and open a TRPV1-like cation conductance, producing slow depolarisation of PVT projection neurons and amplifying their output to accumbens and amygdala. Local NMB infusion should therefore increase arousal and cue-driven seeking, while the NMBR antagonist PD168368 or an Nmbr knockout should blunt stress- and cue-evoked PVT recruitment and reduce anxiety-like behaviour. The cross-inhibition between NMBR and GRPR signalling described in itch circuits (Zhao 2014) predicts the two receptors will also oppose one another here.
Innovation
★★★★☆ 4/5 GRPR signalling in PVT is established but the co-expressed neuromedin B receptor has never been tested there, and the pharmacology to do so already exists.
Tools
Nmbr knockout mice (Ohki-Hamazaki); selective antagonists PD168368 and BIM-23127; agonist neuromedin B; anti-NMBR antibodies; PVT accessible with retro-AAV from accumbens; no widely distributed Nmbr-Cre driver.
References

Direct evidence located at the region

Nmbr Allen ISH at the CCF centroid of PVT

Allen ISH experiment 77332086, section image 77328256 (section 300): the section that contains the CCF centroid of Paraventricular nucleus of the thalamus 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

Direct spatial evidence

MERFISH REGION LOCATOR
PVT MERFISH region locator
Real single-cell MERFISH coordinates for the PVT (Paraventricular nucleus of the thalamus) 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

Nmbr regional expression profile

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

Spatial profile

PVT
1.3
ENTl6a
1.06
PERI6a
0.781
AON
0.781
CM
0.765
STN
0.583
ENTm6
0.56
ECT6b
0.514
IMD
0.477
ECT6a
0.468
TTv
0.463
IAM
0.449
Xi
0.437
AOBgr
0.434
TTd
0.417
EPd
0.409
MD
0.368
IO
0.367
POL
0.362
PF
0.349

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.348
Top-region fraction
0.081
Filter status
PASS

Interpretation limits