Opn5

Opsin-5 (G protein-coupled receptor 136) (G protein-coupled receptor PGR12) (Neuropsin)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: MEPO (Median preoptic nucleus) · Positive regions: 4/554

47.5Discovery Score
41.8Targetability Score
CEvidence grade C
What this means: Opn5: predicted fine-region profile is strict-exclusive, with 4 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in MEPO: evidence, prediction, innovation

Gene function
Opn5 encodes neuropsin (OPN5), a deep-brain UV/violet-sensitive opsin GPCR (peak ~380 nm) that uses 11-cis-retinal and couples to Gi/Go signalling, lowering cAMP. It is bistable and acts as a direct light sensor in skin, retina and hypothalamus.
Region function
The median preoptic nucleus is part of the preoptic thermoregulatory and body-fluid hub, integrating thermal input to drive brown-fat thermogenesis and vasomotor and behavioural thermoregulation, and also controlling thirst, sleep and fever.
Published in this region
direct Zhang et al. 2020 (Nature) showed Opn5 marks glutamatergic warm-sensing preoptic neurons receiving thermoregulatory input; Opn5-null mice have overactive brown adipose tissue, raised body temperature and exaggerated cold-induced thermogenesis, and violet light acutely suppresses BAT temperature in wild-type but not Opn5-null mice. Upton et al. 2021 (Front Neurosci) placed these cells in the QPLOT (Qrfp/Ptger3/LepR/Opn5/Tacr3) thermoregulatory population spanning median and medial preoptic areas.
Predicted function
Prediction: In the median preoptic nucleus OPN5 acts as an intrinsic violet-light sensor on warm-sensitive glutamatergic QPLOT neurons, biasing them towards thermogenesis suppression via Gi-mediated cAMP reduction. Conditional Opn5 deletion in these neurons should raise BAT activity, core temperature and energy expenditure and abolish violet-light suppression of thermogenesis; chemogenetic activation should lower BAT and core temperature and weaken cold defence.
Innovation
★★☆☆☆ 2/5 The Opn5 preoptic thermoregulatory pathway is established, but its specific cellular role and circuit output within the median preoptic nucleus itself remain only partly mapped.
Tools
Opn5-cre and Opn5-null (lacZ knock-in) mice from the Lang laboratory (Zhang 2020, Buhr 2019); violet 380-410 nm LED/fibre photostimulation; Cre-dependent DREADD and ChR2 AAVs; no selective OPN5 pharmacology.
References

Direct evidence located at the region

Opn5 Allen ISH at the CCF centroid of MEPO

Allen ISH experiment 69258226, section image 69150002 (section 148): the section that contains the CCF centroid of Median 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
MEPO MERFISH region locator
Real single-cell MERFISH coordinates for the MEPO (Median 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 69258226, image 69149958 -- target region: MEPO (Median preoptic nucleus)
Allen ISH experiment 69258226, image 69149958 -- target region: MEPO (Median preoptic nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 69258226, image 69149960 -- target region: MEPO (Median preoptic nucleus)
Allen ISH experiment 69258226, image 69149960 -- target region: MEPO (Median preoptic nucleus)

Regional expression figure

Opn5 regional expression profile

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

Spatial profile

MEPO
0.768
AVPV
0.558
AVP
0.238
DG-po
0.198
MPO
0.139
MOBopl
0.132
VLPO
0.13
OV
0.129
ENTm5
0.125
CA3slm
0.121
DG-sg
0.114
ENTm3
0.113
TU
0.103
CA3sr
0.095
LC
0.0946
CA3sp
0.0863
IAD
0.0853
SUT
0.0815
PVHd
0.0782
CA3slu
0.0748

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.404
Top-region fraction
0.185
Filter status
PASS

Interpretation limits