Gper1

G protein-coupled estrogen receptor 1 (Chemoattractant receptor-like 2) (G protein-coupled receptor 30) (Membrane estrogen receptor) (mER)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: MMd (Medial mammillary nucleus, dorsal part) · Positive regions: 53/554

45.0Discovery Score
36.1Targetability Score
CEvidence grade C
What this means: Gper1: fine CCF profile is region-biased toward MMd (top regions: MMd, IG, SSp-m1, AMBd, AIp1); this is a discovery lead, not direct proof.

Function in MMd: evidence, prediction, innovation

Gene function
GPER1 (GPR30) is a seven-transmembrane G protein-coupled receptor that binds 17-beta-estradiol at the plasma and endoplasmic reticulum membrane and signals within seconds through Gs/cAMP-PKA and EGFR transactivation to ERK and PI3K. It mediates the rapid, non-genomic arm of oestrogen action that is independent of the nuclear receptors ERalpha and ERbeta, and can also drive STAT3 phosphorylation.
Region function
The medial mammillary nucleus is the hypothalamic node of the Papez/extended hippocampal circuit: it receives subicular input via the fornix and projects through the mammillothalamic tract to the anterior thalamic nuclei, supporting theta-paced spatial and episodic memory.
Published in this region
inferred No region-specific literature found. The closest findings are in neighbouring hypothalamus: Kwon 2014 showed that the GPER1-selective agonist G-1 triggers STAT3 phosphorylation in hypothalamic neurons and suppresses food intake, while Jiang 2019 found ~80% of activated paraventricular hypothalamic neurons express GPER1.
Predicted function
Prediction: in dorsal medial mammillary neurons GPER1 most plausibly acts as a fast oestrogen-sensitive gain control on the subiculum-to-anterior-thalamus relay, depolarising or facilitating burst firing through Gs/cAMP and thereby coupling gonadal-steroid state to mammillothalamic theta. Local G-1 infusion or Gper1 knockout should shift mammillary firing rate and theta coherence and produce oestrous-cycle-dependent differences in spatial working memory (T-maze alternation, radial arm maze) without affecting gross locomotion.
Innovation
★★★★★ 5/5 GPER1 has been studied extensively in arcuate, PVN and hippocampus but essentially never in the mammillary bodies, despite a well-defined memory circuit and ready pharmacology.
Tools
Selective agonist G-1 and antagonists G-15/G-36; Gper1 knockout mouse lines; commercial anti-GPER1 antibodies; mammillary access via Foxb1-Cre (labels mammillary body neurons) combined with stereotaxic AAV.
References

Direct evidence located at the region

Gper1 Allen ISH at the CCF centroid of MMd

Allen ISH experiment 80342021, section image 80303991 (section 145): the section that contains the CCF centroid of Medial mammillary 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
MMd MERFISH region locator
Real single-cell MERFISH coordinates for the MMd (Medial mammillary 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.

Regional expression figure

Gper1 regional expression profile

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

Spatial profile

MMd
0.707
IG
0.53
SSp-m1
0.502
AMBd
0.488
AIp1
0.487
AUDd1
0.462
ORBvl1
0.46
VISl1
0.458
VISrl1
0.454
SSp-n1
0.445
AUDpo1
0.444
AId1
0.437
CLI
0.429
ECT1
0.427
GU1
0.426
VISam1
0.423
AUDv1
0.422
SSs1
0.415
AUDv2/3
0.413
AUDp1
0.388

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.277
Top-region fraction
0.040
Filter status
PASS

Interpretation limits