Trpm4

Transient receptor potential cation channel subfamily M member 4 (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: MH (Medial habenula) · Positive regions: 47/554

41.9Discovery Score
38.4Targetability Score
CEvidence grade C
What this means: Trpm4: fine CCF profile is region-biased toward MH (top regions: MH, AP, SSp-bfd4, LC, SSp-n4); this is a discovery lead, not direct proof.

Function in MH: evidence, prediction, innovation

Gene function
Trpm4 encodes a Ca2+-activated but Ca2+-impermeable non-selective cation channel of the TRP melastatin family. Rising intracellular Ca2+ opens it to monovalent cations, producing a depolarising Na+ current that paradoxically limits further Ca2+ entry by collapsing the electrical driving force. In excitable cells it supports plateau potentials, bursting and slow afterdepolarisations, and it partners SUR1 in injured CNS tissue.
Region function
The medial habenula is an epithalamic nucleus whose cholinergic (ChAT/Slc17a6) and substance P (Tac1) neurons project almost exclusively through the fasciculus retroflexus to the interpeduncular nucleus. This pathway controls nicotine aversion and withdrawal, anxiety, fear and aversive-memory expression.
Published in this region
inferred No region-specific literature found. The closest relevant finding is Kawai et al. 2025 (Sci Adv), who showed that in MHb neurons nicotinic Ca2+ influx activates a Ca2+-gated chloride conductance which, together with high-threshold Cav channels, holds the membrane near -30 mV to produce a long-lasting refractory period - exactly the class of Ca2+-gated depolarising current TRPM4 mediates elsewhere; Allen ISH detects only trace Trpm4 in MH (energy 0.53 versus 0.38 grey matter).
Predicted function
Prediction: TRPM4 would act in MHb as a Ca2+-activated depolarising conductance downstream of alpha3beta4 nAChRs and high-threshold Ca2+ channels, sustaining the plateau depolarisation underlying the nicotine-evoked long-lasting refractory period and any bursting in these tonically firing neurons. Blocking it with 9-phenanthrol or deleting Trpm4 in MHb should shorten the plateau, restore fast firing after nicotine and so exaggerate nicotine-evoked MHb-IPN output and nicotine aversion. The low mRNA level means an equally plausible outcome is that the relevant conductance is an anoctamin rather than TRPM4.
Innovation
★★★★★ 5/5 There is no habenula TRPM4 literature at all, yet MHb was just shown to depend on Ca2+-activated depolarising conductances, making this an obvious untested candidate.
Tools
Trpm4 global knockout mice; selective blocker 9-phenanthrol and the improved analogue CBA; glibenclamide for SUR1-TRPM4 complexes; TRPM4 antibodies; no Trpm4-Cre line is reported, so cell-type work needs conditional alleles plus ChAT-IRES-Cre (JAX 006410) or Tac1-IRES2-Cre (JAX 021877).
References

Direct evidence located at the region

Trpm4 Allen ISH at the CCF centroid of MH

Allen ISH experiment 69863273, section image 69884304 (section 158): 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 Trpm4Allen reference atlas: MH (structure 483)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Trpm4" or by parcellation_substructure "MH")All genes confined to MH + 3-D brain

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

Trpm4 regional expression profile

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

Spatial profile

MH
2.27
AP
1.75
SSp-bfd4
1.7
LC
1.65
SSp-n4
1.64
DR
1.63
SSp-ul4
1.62
SSp-m4
1.61
SSp-tr4
1.61
RSPv2/3
1.61
SSp-ll4
1.6
VISpor4
1.59
SSp-un4
1.58
AUDpo4
1.58
AD
1.58
SCO
1.57
RSPd2/3
1.57
AUDp4
1.56
VISrl4
1.56
AUDd4
1.56

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.285
Top-region fraction
0.043
Filter status
PASS

Interpretation limits