Tacr1

Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1)

Spatial tier: RESTRICTED · Class: GPCR · Top region: MH (Medial habenula) · Positive regions: 17/554

43.0Discovery Score

41.2Targetability Score

CEvidence grade C

What this means: Tacr1: fine CCF profile is restricted toward MH (top regions: MH, OV, SPFm, MOBipl, CEAc; 17 positive regions); direct spatial validation is still required.

Function in MH: evidence, prediction, innovation

Gene function

TACR1 encodes the neurokinin-1 (NK1) receptor, a class A G-protein-coupled receptor with highest affinity for substance P. It couples to Gq, driving phospholipase C and calcium mobilisation, and it internalises strongly on agonist binding. NK1 antagonists such as aprepitant are clinically effective antiemetics, although they failed as analgesics and antidepressants.

Region function

The medial habenula is a dorsal diencephalic nucleus whose cholinergic, glutamatergic and substance-P neurons project almost exclusively through the fasciculus retroflexus to the interpeduncular nucleus; it controls nicotine aversion and withdrawal, anxiety and mood.

Published in this region

inferred No region-specific literature found. Substance P is a defining transmitter of the dorsal medial habenula - Hsu et al. 2016 showed that tachykinin-expressing dMHb neurons support intracranial self-stimulation and regulate mood-related behaviour - but the NK1 receptors that read this signal have been studied at the target end, in the interpeduncular nucleus, where substance P transmission shapes plasticity alongside nicotinic signalling (Melani & Shen 2019; Eggan & Mineur 2017).

Predicted function

Prediction: NK1 receptors within the medial habenula itself are predicted to act as autoreceptors or local-circuit receptors, so that substance P released from dMHb collaterals feeds back to sustain the tonic firing of neighbouring habenular neurons - a positive-feedback arrangement that would explain how a brief aversive stimulus produces a prolonged habenular response. Local infusion of an NK1 antagonist such as L-733,060 or aprepitant into MH is predicted to shorten the duration of habenular activation after nicotine or footshock and reduce sustained aversive behaviour, while MH-restricted Tacr1 deletion should blunt nicotine withdrawal and anxiety-like behaviour without affecting acute nociception.

Innovation

★★★★☆ 4/5 Substance P biology in the habenulo-interpeduncular pathway is well known but the receptor has only been examined at the interpeduncular target, leaving the habenular side untested despite excellent clinical-grade antagonists.

Tools

Tacr1 knockout and Tacr1 floxed mice, Tacr1-CreER lines; antagonists aprepitant, L-733,060 and RP67580; substance P and the selective agonist GR73632; substance P-saporin for NK1-cell ablation; radioligands and NK1 PET tracers; Tac1-Cre and Chat-Cre for habenular subpopulations.

References

Direct evidence located at the region

Tacr1 Allen ISH at the CCF centroid of MH

Allen ISH experiment 1295, section image 101329863 (section 223): the section that contains the CCF centroid of Medial habenula 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

Allen ISH experiment 79591721, section image 79622442 (section 248): the section that contains the CCF centroid of Medial habenula 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 Tacr1 Allen reference atlas: MH (structure 483)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Tacr1" or by parcellation_substructure "MH")All genes confined to MH + 3-D brain

Direct spatial evidence

MH MERFISH region locator — Real single-cell MERFISH coordinates for the MH (Medial habenula) 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

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

Spatial profile

4.58

2.14

SPFm

2.06

MOBipl

1.66

CEAc

1.64

MOBmi

1.62

NDB

1.61

1.59

MOBgr

1.51

1.49

CEAl

1.48

1.39

MEA

1.39

1.37

MDRNd

1.35

SCop

1.32

PSTN

1.29

CUN

1.26

Evidence and specificity

Evidence status: PREDICTED_FINE
Direct sources: None; predicted localization only
Exclusive threshold: 12 positive regions out of 554
Spatial specificity: 0.283
Top-region fraction: 0.069
Filter status: PASS

Interpretation limits

Cell-type-to-region projection is imputed expression, not direct spatial measurement.
Adult reference atlases do not establish stability across age, sex, strain, state, or disease.
Transcript abundance does not guarantee protein abundance or genetic-tool performance.