Tac2

Spatial tier: STRICT_EXCLUSIVE · Class: OTHER · Top region: MH (Medial habenula) · Positive regions: 1/554

49.0Discovery Score
48.2Targetability Score
CEvidence grade C
What this means: Tac2: predicted fine-region profile is strict-exclusive, with 1 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in MH: evidence, prediction, innovation

Gene function
Tac2 encodes preprotachykinin B, precursor of neurokinin B (NKB). NKB acts preferentially at the Gq-coupled NK3R (Tacr3), driving phospholipase C signalling and excitation. It is known in KNDy neurons controlling GnRH pulsatility and in stress and social-isolation states.
Region function
The medial habenula projects via the fasciculus retroflexus to the interpeduncular nucleus, governing anxiety, fear, nicotine aversion/withdrawal and intrinsic reinforcement.
Published in this region
direct Mar et al. 2012 made Tac2-Cre mice: epithalamic Tac2-lineage labelling is dense and essentially restricted to medial habenula, processes leaving ventrolaterally. Hsu et al. 2016 showed NKB-immunoreactive dorsal MHb neurons support optogenetic intracranial self-stimulation, and dMHb lesions alter tail-suspension immobility. Hashikawa et al. 2020 confirms Tac2 as a top MHb subtype marker in single-cell data; Zelikowsky et al. 2018 tied Tac2/NKB to isolation-induced brain states elsewhere.
Predicted function
Prediction: NKB from MHb terminals excites NK3R-expressing interpeduncular neurons, amplifying aversive/withdrawal signalling atop fast cholinergic-glutamatergic transmission. Conditional Tac2 deletion or NK3R blockade (osanetant/SB-222200) in the MHb-IPN axis should blunt nicotine-withdrawal somatic signs and anxiety without abolishing baseline transmission; senktide in IPN should mimic aversion.
Innovation
★★☆☆☆ 2/5 Tac2 is the canonical MHb marker with functionally characterised neurons, yet the peptide's own action at MHb-IPN synapses is largely untested.
Tools
Tac2-Cre knock-in mice, Tac2-GFP/Tacr3 reporters, NK3R agonist senktide, antagonists osanetant and SB-222200, anti-NKB antibodies; MHb is targeted via fasciculus retroflexus and IPN terminals.
References

Direct evidence located at the region

Tac2 Allen ISH at the CCF centroid of MH

Allen ISH experiment 72339556, section image 72169137 (section 261): 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

Tac2 Allen ISH at the CCF centroid of MH

Allen ISH experiment 77279001, section image 77284584 (section 269): 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

Direct spatial evidence

MERFISH REGION LOCATOR
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

Tac2 regional expression profile

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

Spatial profile

MH
5.62
PD
0.992
CEAl
0.866
VLPO
0.732
LPO
0.713
VMPO
0.711
MPO
0.68
BST
0.633
MPN
0.539
ARH
0.53
AUDpo1
0.439
AUDv1
0.414
CEAm
0.401
ME
0.391
DTN
0.389
CEAc
0.388
RCH
0.376
DMH
0.375
SSp-tr1
0.373
FS
0.361

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.405
Top-region fraction
0.270
Filter status
PASS

Interpretation limits