Grin3b

Glutamate receptor ionotropic, NMDA 3B (GluN3B) (N-methyl-D-aspartate receptor subunit NR3B) (NMDAR3B) (NR3B) (NMDA receptor 4) (Nr4)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: III (Oculomotor nucleus) · Positive regions: 10/554

45.8Discovery Score
41.6Targetability Score
CEvidence grade C
What this means: Grin3b: predicted fine-region profile is strict-exclusive, with 10 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in III: evidence, prediction, innovation

Gene function
Grin3b encodes GluN3B (NR3B), a glycine-binding, non-conventional NMDA receptor subunit. When incorporated into GluN1/GluN2 receptors it acts in a dominant-negative fashion, reducing Ca2+ permeability and Mg2+ block; with GluN1 alone it can form excitatory glycine receptors that are insensitive to glutamate. Its expression is unusually restricted, being concentrated in somatic motoneurons.
Region function
The oculomotor nucleus contains the motoneurons for the medial, superior and inferior rectus, inferior oblique and levator palpebrae, plus the Edinger-Westphal preganglionic neurons, and executes conjugate eye movements, vergence and pupillary/accommodative control.
Published in this region
expression only Nishi et al. 2001 (J Neurosci) reported that NR3B is very restricted to somatic motoneurons of brainstem and spinal cord and explicitly noted weaker expression in oculomotor neurons (and Onuf's nucleus) than in classical somatic motor pools. Fukaya et al. 2005 (Eur J Neurosci) showed the NR2-to-NR3B switchover in somatic motoneurons between P10 and P21. Niemann et al. 2007 (Eur J Neurosci) reported the Grin3b knockout phenotype: mild motor coordination impairment, reduced home-cage activity, increased anxiety-like behaviour and altered social interaction. No study has examined oculomotor function specifically.
Predicted function
Prediction: GluN3B dampens NMDA receptor Ca2+ influx in oculomotor motoneurons, protecting these tonically high-firing cells from excitotoxic Ca2+ load while still allowing glutamatergic drive from premotor burst/tonic neurons. Its relatively low level in the oculomotor nucleus may partly explain the differential vulnerability of motor pools in ALS, where extraocular motoneurons are instead spared by other mechanisms. Knockout should increase NMDA-evoked Ca2+ transients and alter the neural-integrator gain, predicting subtle gaze-holding instability, nystagmus or vergence deficits detectable by high-speed eye tracking rather than gross ocular paralysis.
Innovation
★★★★☆ 4/5 GluN3B is well studied as a motoneuron subunit but nobody has tested it in oculomotor circuits, where quantitative eye-movement readouts are available.
Tools
Grin3b knockout mice (Niemann et al. 2007); Chat-Cre and Isl1-Cre for cranial motoneurons; NMDA receptor pharmacology (MK-801, ifenprodil) and glycine-site ligands, with no GluN3B-selective drug available; anti-GluN3B antibodies used in the Nishi/Fukaya studies; Allen mouse ISH datasets 77869800 (coronal) and 536 (sagittal).
References

Direct evidence located at the region

Grin3b Allen ISH at the CCF centroid of III

Allen ISH experiment 77869800, section image 77876696 (section 178): the section that contains the CCF centroid of Oculomotor nucleus 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
III MERFISH region locator
Real single-cell MERFISH coordinates for the III (Oculomotor nucleus) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 77869800, image 77876748 -- target region: III (Oculomotor nucleus)
Allen ISH experiment 77869800, image 77876748 -- target region: III (Oculomotor nucleus)
DIRECT ALLEN ISH
Allen ISH experiment 77869800, image 77876754 -- target region: III (Oculomotor nucleus)
Allen ISH experiment 77869800, image 77876754 -- target region: III (Oculomotor nucleus)

Regional expression figure

Grin3b regional expression profile

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

Spatial profile

III
1.48
V
1.32
VI
1.25
XII
0.864
VII
0.779
DMX
0.749
I5
0.625
MH
0.468
AMBd
0.393
P5
0.387
AD
0.359
SUT
0.314
PPY
0.269
y
0.26
LIN
0.236
PRP
0.234
IRN
0.232
MV
0.224
PGRNd
0.222
ND
0.222

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.387
Top-region fraction
0.105
Filter status
PASS

Interpretation limits