Htr1d

5-hydroxytryptamine receptor 1D (5-HT-1D) (5-HT1D) (Serotonin receptor 1D)

Spatial tier: RESTRICTED · Class: GPCR · Top region: OT (Olfactory tubercle) · Positive regions: 27/554

44.7Discovery Score
39.6Targetability Score
CEvidence grade C
What this means: Htr1d: fine CCF profile is restricted toward OT (top regions: OT, PVT, CP, ACB, DR; 27 positive regions); direct spatial validation is still required.

Function in OT: evidence, prediction, innovation

Gene function
Htr1d encodes the 5-HT1D serotonin receptor, a Gi/Go-coupled GPCR that lowers cAMP and suppresses transmitter release at nerve terminals. It is pharmacologically near-identical to 5-HT1B and is a triptan antimigraine target; brain expression is low and far more spatially restricted than Htr1b.
Region function
The olfactory tubercle is the olfactory ventral striatum, receiving direct mitral/tufted cell and dense VTA dopamine input; its D1 and D2 medium spiny neurons encode odour-reward associations, hedonics and motivated approach.
Published in this region
expression only Expression only. Bach et al. 1993 found the highest rat 5-HT1D mRNA signal by in situ hybridization in the pyramidal layer of the olfactory tubercle, plus caudate and accumbens. Bonaventure et al. 1998 confirmed in guinea pig that 5-HT1D mRNA is restricted and dominated by the olfactory tubercle, while 5-HT1D binding sites fell below detection, implying very low protein density. No physiological or behavioural manipulation in OT exists.
Predicted function
Prediction: OT 5-HT1D acts as an inhibitory brake on raphe serotonergic modulation, either presynaptically on glutamatergic and dopaminergic terminals or on MSN somata, damping cAMP/PKA signalling downstream of D1 receptors. Local blockade with BRL-15572 or conditional deletion should disinhibit OT output and enhance odour-cued approach and reward learning; agonism should blunt odour-driven motivation. Effects will be small because 5-HT1B dominates the same tissue.
Innovation
★★★★☆ 4/5 OT is the highest-expressing structure for Htr1d mRNA, yet no functional study has targeted the receptor there.
Tools
BRL-15572 (5-HT1D antagonist) and SB-216641 (5-HT1B antagonist) permit subtype dissection; no Htr1d-Cre line published; OT cell types accessible with Drd1-Cre and Adora2a-Cre plus Cre-dependent AAV; Htr1d knockout/conditional alleles listed at MGI/IMPC.
References

Direct evidence located at the region

Htr1d Allen ISH at the CCF centroid of OT

Allen ISH experiment 71393418, section image 71244323 (section 148): the section that contains the CCF centroid of Olfactory tubercle 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

Look it up yourself: Allen Mouse Brain ISH for Htr1dAllen reference atlas: OT (structure 754)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Htr1d" or by parcellation_substructure "OT")All genes confined to OT + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
OT MERFISH region locator
Real single-cell MERFISH coordinates for the OT (Olfactory tubercle) 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

Htr1d regional expression profile

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

Spatial profile

OT
1.46
PVT
1.41
CP
1.26
ACB
0.998
DR
0.984
RO
0.906
AOBgr
0.85
Pa5
0.775
FS
0.751
CEAl
0.621
TRS
0.618
PIR
0.614
EPd
0.607
LC
0.593
CEAc
0.551
MOp6b
0.505
STN
0.482
SF
0.471
AIp6b
0.47
PSTN
0.457

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.322
Top-region fraction
0.056
Filter status
PASS

Interpretation limits