Nppa

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

50.3Discovery Score
48.7Targetability Score
CEvidence grade C
What this means: Nppa: 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
Nppa encodes atrial natriuretic peptide (ANP), a short secreted peptide hormone best known for lowering blood pressure. It acts on the receptor guanylyl cyclase NPR-A (guanylyl cyclase-A), which makes cGMP; downstream effectors include protein kinase G, cGMP-gated channels and cGMP-stimulated phosphodiesterases.
Region function
The medial habenula is an epithalamic relay whose cholinergic/substance P neurons project almost exclusively through the fasciculus retroflexus to the interpeduncular nucleus. This MHb-IPN axis sets nicotine aversion and withdrawal, fear memory expression, anxiety and negative affect.
Published in this region
direct Hu et al. 2012 (PNAS) studied ANP signalling directly in the MHb-IPN pathway: ANP raises cGMP in IPN slices, and both ANP and BNP profoundly block optogenetically evoked glutamate release from MHb terminals. The block requires phosphodiesterase 2A, which is richly expressed in MHb axon terminals and depletes cAMP when stimulated by cGMP, and is reversed by directly activating PKA; infusing ANP into the IPN enhanced stress-induced analgesia. Kawata et al. 1985 and Langub et al. 1995 mapped ANP peptide and precursor mRNA across rat brain.
Predicted function
Prediction: ANP made by MHb neurons acts as an autocrine or terminal-field brake that converts cGMP signals into presynaptic cAMP depletion and shuts down glutamate release onto the IPN. Deleting Nppa should remove this brake, increasing MHb-IPN transmission, reducing stress-induced analgesia and plausibly increasing anxiety and nicotine withdrawal severity; PDE2A inhibitors should phenocopy the knockout at the synaptic level.
Innovation
★★★☆☆ 3/5 The peptide's action on this synapse is established pharmacologically, but no one has deleted Nppa from MHb neurons themselves or tested its behavioural necessity.
Tools
Nppa knockout mice (Jackson Laboratory) and floxed Nppa alleles; synthetic ANP and BNP peptides; NPR-A antagonist A71915 and anantin; PDE2A inhibitors BAY 60-7550 and PF-05180999; anti-ANP antibodies and cGMP biosensors.
References

Direct evidence located at the region

No Allen ISH section could be located at this region's centroid for the recorded experiments.

Look it up yourself: Allen Mouse Brain ISH for NppaAllen reference atlas: MH (structure 483)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Nppa" 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

Nppa regional expression profile

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

Spatial profile

MH
2.81
MOBopl
0.54
AOBmi
0.363
TMd
0.341
RT
0.312
LH
0.3
AP
0.295
AOBgr
0.253
AOBgl
0.232
ORBm1
0.225
RL
0.211
PVp
0.191
DMX
0.16
AVPV
0.147
MOBmi
0.144
FC
0.14
ORBvl1
0.132
MMme
0.13
PS
0.129
IPR
0.112

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.452
Top-region fraction
0.304
Filter status
PASS

Interpretation limits