Ltb4r1

Leukotriene B4 receptor 1 (LTB4-R 1) (LTB4-R1)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: TMd (Tuberomammillary nucleus, dorsal part) · Positive regions: 11/554

44.9Discovery Score
36.1Targetability Score
CEvidence grade C
What this means: Ltb4r1: predicted fine-region profile is strict-exclusive, with 11 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in TMd: evidence, prediction, innovation

Gene function
Ltb4r1 encodes BLT1, the high-affinity GPCR for leukotriene B4, a 5-lipoxygenase product; it also binds resolvin E1. Coupling to Gi and G16, it drives chemotaxis, Ca2+ mobilization and NF-kB signaling in neutrophils, T cells and macrophages, and is targeted by etalocib (LY293111).
Region function
The dorsal tuberomammillary nucleus contains the brain's histaminergic neurons, which project brain-wide to promote wakefulness and arousal and suppress feeding, and are silenced during sleep.
Published in this region
none No region-specific literature found. BLT1 is primarily a leukocyte receptor (Tager 2003), is up-regulated in cortical neurons and glia after subarachnoid haemorrhage (Ye 2016), is detected in human basal forebrain and hippocampus and elevated in Alzheimer's disease (Emre 2020), and intracerebroventricular LTB4 stimulates the HPA axis via BLT1 in rats (Zhang 2010), but none reach histaminergic TMN neurons.
Predicted function
Prediction: BLT1 on histaminergic TMN neurons would convert an inflammatory lipid signal, LTB4 from leukocytes or microglia, into altered arousal, coupling systemic inflammation to sickness somnolence via Gi. Local LTB4 infusion should change sleep-wake architecture; Ltb4r1 deletion in Hdc-Cre neurons should blunt LPS-induced wakefulness changes.
Innovation
★★★★☆ 4/5 A potent, druggable receptor with knockout mice and antagonists, never examined in the histaminergic system that governs arousal.
Tools
Ltb4r1 knockout mice (BLT1-/-); agonist LTB4; antagonists U-75302, CP-105696, LY293111 (etalocib); anti-BLT1 antibodies used in brain (Ye 2016; Emre 2020); Hdc-Cre for TMN histamine neurons.
References

Direct evidence located at the region

Ltb4r1 Allen ISH at the CCF centroid of TMd

Allen ISH experiment 68744188, section image 68722203 (section 145): the section that contains the CCF centroid of Tuberomammillary nucleus, dorsal part 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
TMd MERFISH region locator
Real single-cell MERFISH coordinates for the TMd (Tuberomammillary nucleus, dorsal part) 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 68744188, image 68722161 -- target region: TMd (Tuberomammillary nucleus, dorsal part)
Allen ISH experiment 68744188, image 68722161 -- target region: TMd (Tuberomammillary nucleus, dorsal part)
DIRECT ALLEN ISH
Allen ISH experiment 68744188, image 68722163 -- target region: TMd (Tuberomammillary nucleus, dorsal part)
Allen ISH experiment 68744188, image 68722163 -- target region: TMd (Tuberomammillary nucleus, dorsal part)

Regional expression figure

Ltb4r1 regional expression profile

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

Spatial profile

TMd
0.251
PMd
0.21
MMme
0.144
MMl
0.143
MMp
0.137
MMm
0.137
PBG
0.136
ME
0.135
PVp
0.123
EW
0.114
OV
0.113
MMd
0.1
ENTl6a
0.0945
Su3
0.0912
PERI5
0.0912
ProS
0.0907
ENTl5
0.0896
PT
0.0848
SH
0.083
AVPV
0.082

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.346
Top-region fraction
0.098
Filter status
PASS

Interpretation limits