Brs3

Bombesin receptor subtype-3 (BRS-3)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: PD (Posterodorsal preoptic nucleus) · Positive regions: 10/554

49.5Discovery Score
41.8Targetability Score
CEvidence grade C
What this means: Brs3: predicted fine-region profile is strict-exclusive, with 10 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in PD: evidence, prediction, innovation

Gene function
BRS3 is an orphan class A bombesin-family GPCR, Gq/G11-coupled and calcium-mobilising; no endogenous ligand is confirmed; agonists MK-5046 and Bag-1 and antagonist Bantag-1 exist. Brs3-null mice are obese with mildly raised food intake, reduced metabolic rate and lower temperature, a long-standing anti-obesity target.
Region function
The posterodorsal preoptic nucleus is a small caudal cluster bordering parastrial nucleus, BNST and anterior PVH, controlling temperature, sleep and male sexual behaviour.
Published in this region
direct Pinol et al. 2021: preoptic Brs3 neurons are cold-activated; activation raises body temperature, heart rate and blood pressure via BAT thermogenesis and PVH/DMH sympathetic output, inhibition lowers temperature, silencing destabilises the set point, though manipulations spanned MnPO/MPO, not this nucleus. Pinol et al. 2018 and Maruyama et al. 2018 found parallel DMH/MPA Brs3 thermogenic and energy-expenditure roles.
Predicted function
Prediction: PD Brs3 neurons are a caudal node of this warm-defence module linking thermogenesis to arousal and reproductive state. Gq coupling predicts local MK-5046 raises core temperature and heart rate, while Bantag-1 or PD DREADD inhibition blunts cold defence and stress hyperthermia. A sex-specific role in copulation hyperthermia is testable.
Innovation
★★☆☆☆ 2/5 BRS3 is well studied in preoptic and DMH thermoregulation, so only posterodorsal specificity is new.
Tools
Brs3-Cre and Brs3-null mice (Pinol et al. 2018, 2021); agonists MK-5046 and Bag-1, antagonist Bantag-1; Cre-dependent AAV DREADDs/ChR2 and photometry work here; Esr1-Cre and Vgat/Vglut2-Cre available.
References

Direct evidence located at the region

Brs3 Allen ISH at the CCF centroid of PD

Allen ISH experiment 70560328, section image 70368137 (section 320): the section that contains the CCF centroid of Posterodorsal preoptic nucleus 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
PD MERFISH region locator
Real single-cell MERFISH coordinates for the PD (Posterodorsal preoptic nucleus) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 70560328, image 70368093 -- target region: PD (Posterodorsal preoptic nucleus)
Allen ISH experiment 70560328, image 70368093 -- target region: PD (Posterodorsal preoptic nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 70560328, image 70368695 -- target region: PD (Posterodorsal preoptic nucleus)
Allen ISH experiment 70560328, image 70368695 -- target region: PD (Posterodorsal preoptic nucleus)

Regional expression figure

Brs3 regional expression profile

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

Spatial profile

PD
1.13
MPN
0.654
MEPO
0.652
VMPO
0.63
ARH
0.493
DMH
0.44
AVPV
0.408
MPO
0.32
BST
0.287
VLPO
0.241
PVpo
0.215
ME
0.206
VMH
0.176
LC
0.172
PS
0.164
CEAm
0.145
MEA
0.145
PVH
0.137
TMv
0.133
AVP
0.131

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.406
Top-region fraction
0.118
Filter status
PASS

Interpretation limits