Gabre

Gamma-aminobutyric acid receptor subunit epsilon (GABA(A) receptor subunit epsilon)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: ARH (Arcuate hypothalamic nucleus) · Positive regions: 35/554

44.7Discovery Score
42.5Targetability Score
CEvidence grade C
What this means: Gabre: fine CCF profile is region-biased toward ARH (top regions: ARH, MEPO, PD, DMH, AVPV); this is a discovery lead, not direct proof.

Function in ARH: evidence, prediction, innovation

Gene function
Gabre encodes the epsilon subunit of the GABA-A receptor, a pentameric GABA-gated chloride channel. Epsilon-containing receptors show large agonist-independent (spontaneous) openings, fast desensitisation and resistance to potentiation by propofol and anabolic androgenic steroids. The gene lies in the X-linked Gabra3/Gabrq cluster and is restricted to certain hypothalamic and aminergic neurons.
Region function
The arcuate hypothalamic nucleus sits beside the median eminence and reads circulating leptin, insulin and ghrelin through a leaky barrier. Its AgRP/NPY, POMC and Kiss1 neurons set food intake, energy expenditure and neuroendocrine output.
Published in this region
expression only No functional study of Gabre in the ARH. Moragues et al. 2003 mapped epsilon across rat hypothalamic peptidergic populations, finding over 90% co-expression with hypocretin, oxytocin, GnRH and MCH neurons but under 10% with CART neurons, the marker that in ARH labels POMC cells; Sergeeva et al. 2005 recorded propofol-resistant IPSCs in epsilon-positive tuberomammillary and orexin neurons; Wang Z et al. 2024 made a Gabre-Cre line and showed preoptic Gabre neurons set body temperature and heart rate.
Predicted function
Prediction: in ARH, epsilon-containing receptors would supply a standing, ligand-independent chloride leak setting resting potential and firing threshold in a defined neuron subset, and would make those cells relatively propofol- and neurosteroid-insensitive. Chemogenetic activation of ARH Gabre neurons via the existing Gabre-Cre line should alter food intake and thermogenesis; Gabre deletion should depolarise these cells and produce hyperphagia or altered energy expenditure plus an anaesthetic-sensitivity shift.
Innovation
★★★★☆ 4/5 A Gabre-Cre mouse now exists but has only been used in the preoptic area, leaving the arcuate Gabre population unexamined despite clear relevance to feeding.
Tools
Gabre-Cre knock-in mouse (Wang Z 2024) with standard DREADD and ChR2 AAVs; anti-GABA-A epsilon antibodies and ISH probes; propofol- and steroid-insensitive currents (Jones 2006) as an electrophysiological signature; Agrp-Flp or Pomc-Flp for intersectional targeting.
References

Direct evidence located at the region

Gabre Allen ISH at the CCF centroid of ARH

Allen ISH experiment 75749417, section image 75647271 (section 266): the section that contains the CCF centroid of Arcuate hypothalamic 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
ARH MERFISH region locator
Real single-cell MERFISH coordinates for the ARH (Arcuate hypothalamic 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.

Regional expression figure

Gabre regional expression profile

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

Spatial profile

ARH
3.65
MEPO
3.21
PD
2.52
DMH
2.29
AVPV
2.27
VMPO
2.21
MPN
2.16
OV
2.05
LC
1.88
PVa
1.85
PVpo
1.84
SBPV
1.74
ME
1.66
MPO
1.49
AVP
1.44
VLPO
1.39
PVH
1.36
RO
1.34
SCH
1.33
VMH
1.27

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.334
Top-region fraction
0.053
Filter status
PASS

Interpretation limits