Asic4

Acid-sensing ion channel 4 (ASIC4) (Amiloride-sensitive cation channel 4)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: SCsg (Superior colliculus, superficial gray layer) · Positive regions: 37/554

44.3Discovery Score

40.3Targetability Score

CEvidence grade C

What this means: Asic4: fine CCF profile is region-biased toward SCsg (top regions: SCsg, CP, OT, IPR, ACB); this is a discovery lead, not direct proof.

Function in SCsg: evidence, prediction, innovation

Gene function

ASIC4 is a member of the acid-sensing ion channel family of proton-gated sodium channels (ENaC/degenerin superfamily). Unlike ASIC1a or ASIC3 it is not itself gated by protons in heterologous systems; instead it acts as a modulatory subunit that changes the surface expression and proton sensitivity of other ASICs, especially ASIC1a.

Region function

The superficial gray layer of the superior colliculus is the main retinorecipient midbrain visual layer; its neurons are direction- and orientation-selective, are modulated by locomotion and reward, and feed orienting, looming-evoked defence and visuomotor behaviour.

Published in this region

expression only Hoshikawa 2017 mapped Asic4 transcripts by in situ hybridisation and Asic4-lacZ reporter across the adult mouse brain and listed the superior colliculus among the structures where ASIC4 mRNA is preferentially concentrated; Lin 2015, using an Asic4-CreERT2 knock-in reporter, showed ASIC4 is expressed mainly in calretinin/VIP interneurons and NG2 glia and found no deficit in fear learning, so no function has been assigned in the colliculus.

Predicted function

Prediction: in the superficial superior colliculus ASIC4 most plausibly sits in calretinin/VIP-type inhibitory interneurons and NG2 glia, where it would set ASIC1a surface levels and thus how strongly these cells respond to the activity-dependent acid transients released with synaptic vesicles during intense visual drive. Asic4 deletion should raise ASIC1a-mediated currents in collicular interneurons, sharpening or destabilising inhibitory gain; predicted behavioural readouts are altered looming-evoked escape/freezing thresholds and changed visual contrast sensitivity rather than gross blindness.

Innovation

★★★★★ 5/5 Expression in the colliculus is documented but nobody has tested ASIC4 function in any visual circuit, and a Cre knock-in line already exists.

Tools

Asic4-CreERT2 knock-in/knockout mice (Lin 2015) and Asic4-lacZ (KOMP) reporter; amiloride and psalmotoxin-1 for ASIC pharmacology (no ASIC4-selective drug); anti-ASIC4 antibodies; collicular interneuron access via Calb2-Cre and Vip-Cre.

References

Direct evidence located at the region

Asic4 Allen ISH at the CCF centroid of SCsg

Allen ISH experiment 71924089, section image 71757166 (section 181): the section that contains the CCF centroid of Superior colliculus, superficial gray layer 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 Asic4 Allen reference atlas: SCsg (structure 842)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Asic4" or by parcellation_substructure "SCsg")All genes confined to SCsg + 3-D brain

Direct spatial evidence

SCsg MERFISH region locator — Real single-cell MERFISH coordinates for the SCsg (Superior colliculus, superficial gray layer) 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

SCsg

2.28

2.09

2.01

IPR

1.82

ACB

1.7

IPC

1.64

SCop

1.55

SCzo

1.52

1.48

1.38

AIp6b

1.34

IPI

1.27

1.25

SCig

1.04

GU6b

1.04

CLA

1.03

NOT

1.03

AIp6a

1.02

NPC

0.992

0.979

Evidence and specificity

Evidence status: PREDICTED_FINE
Direct sources: None; predicted localization only
Exclusive threshold: 12 positive regions out of 554
Spatial specificity: 0.309
Top-region fraction: 0.046
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.