Pth2r

Parathyroid hormone 2 receptor (PTH2 receptor)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: MGd (Medial geniculate complex, dorsal part) · Positive regions: 35/554

43.9Discovery Score
40.3Targetability Score
CEvidence grade C
What this means: Pth2r: fine CCF profile is region-biased toward MGd (top regions: MGd, SGN, PBG, POL, PIL); this is a discovery lead, not direct proof.

Function in MGd: evidence, prediction, innovation

Gene function
Pth2r encodes the parathyroid hormone 2 receptor, a class B secretin-family GPCR coupling to Gs and raising cAMP. Its endogenous brain ligand is tuberoinfundibular peptide of 39 residues (TIP39), made by only two neuron groups: the subparafascicular area and the medial paralemniscal nucleus. The pair modulates limbic, neuroendocrine, nociceptive and auditory circuits; knockouts alter fear and stress hormones.
Region function
The dorsal medial geniculate is non-lemniscal auditory thalamus: broadly tuned, multisensory and plastic, projecting to belt auditory cortex and amygdala, the pathway used for auditory fear conditioning.
Published in this region
direct Faber 2007 mapped PTH2R mRNA, lacZ reporter and immunoreactive fibres in mouse, listing the medial geniculate body among regions of abundant PTH2R with matching TIP39 innervation. Dobolyi 2003 showed by lesion that these fibres originate in the medial paralemniscal nucleus, not the subparafascicular group, and Palkovits 2009 found 105 dB noise drives c-fos in ~80% of medial paralemniscal TIP39 neurons. Bago 2009 confirmed this in macaque. Allen ISH gives MGd 0.61 versus 0.28 for grey matter.
Predicted function
Prediction: PTH2R in MGd is the target of a loud-sound-activated peptidergic projection from the medial paralemniscal nucleus, acting through Gs-cAMP to gain-modulate non-lemniscal relay during acoustic stress. Deleting Pth2r in MGd, or chemogenetically silencing medial paralemniscal TIP39 neurons, should spare thresholds but reduce noise-induced enhancement of auditory-cued fear learning.
Innovation
★★☆☆☆ 2/5 TIP39-PTH2R anatomy in the medial geniculate is well described, but its auditory function has never been tested.
Tools
PTH2R-lacZ knock-in reporter and PTH2R knockout mice (Faber 2007; Dimitrov 2010); TIP39 knockout mice (Fegley 2008); synthetic TIP39 peptide; PTH2R and TIP39 antibodies.
References

Direct evidence located at the region

Pth2r Allen ISH at the CCF centroid of MGd

Allen ISH experiment 69863250, section image 69883998 (section 152): the section that contains the CCF centroid of Medial geniculate complex, dorsal part 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 Pth2rAllen reference atlas: MGd (structure 1072)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Pth2r" or by parcellation_substructure "MGd")All genes confined to MGd + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
MGd MERFISH region locator
Real single-cell MERFISH coordinates for the MGd (Medial geniculate complex, dorsal part) 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

Pth2r regional expression profile

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

Spatial profile

MGd
2.39
SGN
2.37
PBG
2
POL
1.84
PIL
1.63
ENTm5
1.58
ECT6b
1.36
ENTm3
1.35
PoT
1.29
MGv
1.25
RH
1.25
TEa6b
1.2
PP
1.2
ECT6a
1.07
VISpor6b
1.06
PERI6a
1.03
ACAv6b
1.02
MGm
1.01
ENTm6
0.981
COApm
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
0.299
Top-region fraction
0.046
Filter status
PASS

Interpretation limits