Chrna7

Neuronal acetylcholine receptor subunit alpha-7 (nAChR7) (Nicotinic acetylcholine receptor subunit alpha-7)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: CA2sp (Field CA2, pyramidal layer) · Positive regions: 43/554

41.7Discovery Score
40.5Targetability Score
CEvidence grade C
What this means: Chrna7: fine CCF profile is region-biased toward CA2sp (top regions: CA2sp, CA1sp, CA2so, DG-po, PDTg); this is a discovery lead, not direct proof.

Function in CA2sp: evidence, prediction, innovation

Gene function
Chrna7 encodes the alpha7 nicotinic acetylcholine receptor subunit, which forms homopentameric ligand-gated channels with unusually high Ca2+ permeability and fast desensitisation. Alpha7 receptors bind alpha-bungarotoxin, sit largely presynaptically and on interneurons, and couple ACh release to Ca2+-dependent transmitter release and CaMKII/CREB plasticity signalling. Orr-Urtreger et al. 1997 showed knockout mice lose all hippocampal alpha-bungarotoxin binding and fast nicotinic currents.
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
inferred Nicotinic signalling in CA2 is established but not yet resolved to alpha7. Pimpinella et al. 2021 showed septal cholinergic input drives CA2 principal cells by nAChR-mediated disinhibition and that an nAChR antagonist infused into CA2 impairs social novelty discrimination; Benoy et al. 2021 found nicotinic receptors maintain carbachol-LTD at CA2 synapses. Allen ISH (experiments 69237107, 74511738) shows clear Chrna7 in the CA2 pyramidal layer (energy ~5.0 vs 2.2 whole brain), and Frazier et al. 1998 localised functional alpha7 currents to hippocampal interneurons.
Predicted function
Prediction: alpha7 receptors on CA2-targeting interneurons and presynaptic terminals are the most likely mediators of the septal cholinergic disinhibition Pimpinella described, providing Ca2+ influx that transiently lifts perisomatic inhibition so CA2 cells fire during encounters with novel conspecifics. Local methyllycaconitine or CA2-restricted Chrna7 deletion should impair social novelty discrimination while sparing object memory; the agonist PNU-282987 or PAM PNU-120596 should enhance it and increase ripple-associated CA2 firing.
Innovation
★★☆☆☆ 2/5 Alpha7 in hippocampus is heavily studied and CA2 nicotinic disinhibition is already published; only the subunit-specific CA2-restricted causal test is missing.
Tools
Chrna7 knockout mice (JAX 003232, B6.129S7-Chrna7tm1Bay/J) and floxed Chrna7 alleles; agonists PNU-282987 and choline; PAMs PNU-120596 and JWX-A0108; antagonists methyllycaconitine and alpha-bungarotoxin; fluorescent alpha-conotoxin probes; Amigo2-Cre for CA2 and ChAT-Cre for septal input.
References

Direct evidence located at the region

Chrna7 Allen ISH at the CCF centroid of CA2sp

Allen ISH experiment 74511738, section image 74362001 (section 250): 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

Look it up yourself: Allen Mouse Brain ISH for Chrna7Allen reference atlas: CA2sp (structure 446)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Chrna7" or by parcellation_substructure "CA2sp")All genes confined to CA2sp + 3-D brain

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

Chrna7 regional expression profile

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

Spatial profile

CA2sp
4.35
CA1sp
3.79
CA2so
3.54
DG-po
3.41
PDTg
3.33
CA1so
3.19
PA
3.01
CA3sp
2.95
DTN
2.94
DG-sg
2.9
CA1sr
2.85
CA3slu
2.74
PERI6a
2.67
CP
2.61
ECT6a
2.6
SCsg
2.58
ECT6b
2.55
ICc
2.53
ENTl6a
2.5
BMAp
2.47

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.280
Top-region fraction
0.042
Filter status
PASS

Interpretation limits