Chrna1

Acetylcholine receptor subunit alpha

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: CA2sp (Field CA2, pyramidal layer) · Positive regions: 35/554

44.2Discovery Score
34.2Targetability Score
CEvidence grade C
What this means: Chrna1: fine CCF profile is region-biased toward CA2sp (top regions: CA2sp, CA3sp, CA3so, CA3slu, ENTm3); this is a discovery lead, not direct proof.

Function in CA2sp: evidence, prediction, innovation

Gene function
Chrna1 encodes the alpha1 subunit of the muscle-type nicotinic acetylcholine receptor, a pentameric ligand-gated cation channel that mediates fast depolarisation at the neuromuscular junction. The alpha1 subunit carries the principal ACh-binding face and the alpha-bungarotoxin site; its mutation causes congenital myasthenic syndromes and it is the main autoantigen in myasthenia gravis. It is not normally regarded as a CNS receptor subunit.
Region function
Hippocampal CA2 is a small pyramidal subfield between CA3 and CA1 that receives dense entorhinal layer II and septal/supramammillary input and is required for social recognition memory and for pacing sharp-wave ripples.
Published in this region
none No region-specific literature found. The closest evidence is anatomical and weak: Allen coronal ISH (experiment 75551465) shows high but spatially near-uniform Chrna1 signal across CA2, CA1, CA3 and ARH (energy 6-9), a pattern typical of probe background, while the sagittal experiment 100146096 shows essentially nothing (0.03-0.09); the CA2 proteome of Gerber et al. 2019 does not report alpha1 protein.
Predicted function
Prediction: genuine alpha1 protein in CA2 is unlikely, so the first experiment should be validation (RNAscope plus alpha-bungarotoxin binding with alpha7-knockout controls) rather than manipulation. If confirmed, the plausible role is a non-canonical nicotinic conductance, or an assembly/chaperone contribution to heteromeric receptors on CA2 pyramidal cells, which receive strong septal cholinergic input. Conditional deletion would then reduce a bungarotoxin-sensitive, alpha7-independent current and slightly blunt cholinergic facilitation of CA2 firing.
Innovation
★★★☆☆ 3/5 Nobody has studied Chrna1 in hippocampus, but the atlas signal looks like background, so novelty is high and so is the risk of nothing being there.
Tools
Alpha-bungarotoxin and muscle-nAChR antibodies (both cross-react with alpha7, so alpha7-knockout controls are required); Chrna1 mutant alleles from congenital-myasthenia models; Amigo2-Cre for CA2-restricted manipulation. No CNS-specific driver or selective ligand known.
References

Direct evidence located at the region

Chrna1 Allen ISH at the CCF centroid of CA2sp

Allen ISH experiment 75551465, section image 75486689 (section 240): the section that contains the CCF centroid of Field CA2, pyramidal 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

Direct spatial evidence

MERFISH REGION LOCATOR
CA2sp MERFISH region locator
Real single-cell MERFISH coordinates for the CA2sp (Field CA2, pyramidal 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

Chrna1 regional expression profile

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

Spatial profile

CA2sp
0.164
CA3sp
0.154
CA3so
0.152
CA3slu
0.146
ENTm3
0.145
ENTm5
0.127
ENTm2
0.119
PAR
0.103
CA2so
0.102
RSPv5
0.101
POST
0.0965
ENTl3
0.093
CA3sr
0.0902
PRE
0.0838
RSPv2/3
0.075
CA1sp
0.0743
ENTl5
0.0727
RSPd5
0.0718
ENTl2
0.0701
PERI5
0.0697

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
0.045
Filter status
PASS

Interpretation limits