Htr3b

5-hydroxytryptamine receptor 3B (5-HT3-B) (5-HT3B) (Serotonin receptor 3B)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: ARH (Arcuate hypothalamic nucleus) · Positive regions: 1/554

48.6Discovery Score
38.5Targetability Score
CEvidence grade C
What this means: Htr3b: predicted fine-region profile is strict-exclusive, with 1 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in ARH: evidence, prediction, innovation

Gene function
Htr3b encodes the 5-HT3B subunit of the 5-HT3 receptor, the only ionotropic serotonin receptor, a pentameric Cys-loop cation channel. 5-HT3B cannot form homomers but assembles with 5-HT3A into heteromers with much larger conductance and altered calcium permeability. Serotonin-gated opening depolarises the neuron; this receptor is the target of anti-emetic setrons.
Region function
The arcuate nucleus integrates blood-borne metabolic signals through AgRP/NPY, POMC, dopaminergic and GABAergic populations to control appetite, body weight and pituitary output.
Published in this region
expression only Lavoie et al. 2024 (Neuroendocrinology) reported that mouse ARH Htr3b is confined to the dorsal ARH and expressed almost exclusively by Crabp1-positive GABAergic neurons, a population regulated by fasting and liraglutide; no function was tested. Hisadome et al. 2009 (Neuroscience) showed ARH POMC neurons respond heterogeneously to serotonin, establishing serotonergic control of ARH but via metabotropic receptors.
Predicted function
Prediction: 5-HT3A/3B channels give dorsal-ARH Crabp1 GABAergic neurons a fast excitatory serotonin input alongside slow 5-HT2C actions on POMC and AgRP cells. Because these cells are GABAergic, 5-HT3 agonism (mCPBG) should increase local inhibition of POMC or AgRP neurons and shift food intake, while Htr3b deletion or ondansetron should blunt anorectic responses to serotonergic drugs. Chemogenetic activation of Htr3b/Crabp1 cells should alter feeding and possibly nausea-like avoidance.
Innovation
★★★★☆ 4/5 Only a single 2024 paper reports Htr3b in the ARH and nobody has tested what this fast serotonin channel does in a nucleus otherwise dominated by metabotropic 5-HT receptor work.
Tools
Htr3b knockout mice, Htr3a-EGFP (GENSAT) and Htr3a-Cre lines for the obligatory partner subunit, antagonists ondansetron/granisetron/tropisetron, agonist mCPBG, Crabp1 as an intersectional marker for the ARH population.
References

Direct evidence located at the region

Htr3b Allen ISH at the CCF centroid of ARH

Allen ISH experiment 74641318, section image 74531978 (section 264): 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.
DIRECT ALLEN ISH
Allen ISH experiment 74641318, image 74531976 -- target region: ARH (Arcuate hypothalamic nucleus)
Allen ISH experiment 74641318, image 74531976 -- target region: ARH (Arcuate hypothalamic nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 74641318, image 74531972 -- target region: ARH (Arcuate hypothalamic nucleus)
Allen ISH experiment 74641318, image 74531972 -- target region: ARH (Arcuate hypothalamic nucleus)

Regional expression figure

Htr3b regional expression profile

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

Spatial profile

ARH
0.187
ME
0.039
LC
0.033
VMH
0.0298
DMH
0.0244
PVi
0.0226
SLC
0.0211
IO
0.0208
SSp-un1
0.0194
SSp-ll1
0.0192
SBPV
0.0191
SSp-ul1
0.0189
VISa1
0.0187
VISC1
0.0181
AUDpo1
0.0176
VISal1
0.0175
VISli1
0.0174
SSp-tr1
0.0171
VISrl1
0.0165
VISpm1
0.0161

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.359
Top-region fraction
0.205
Filter status
PASS

Interpretation limits