Ryr1

Ryanodine receptor 1 (RYR-1) (RyR1) (Skeletal muscle calcium release channel) (Skeletal muscle ryanodine receptor) (Skeletal muscle-type ryanodine receptor) (Type 1 ryanodine receptor)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: CP (Caudoputamen) · Positive regions: 38/554

42.3Discovery Score
39.7Targetability Score
CEvidence grade C
What this means: Ryr1: fine CCF profile is region-biased toward CP (top regions: CP, OT, ACB, DG-po, CEAc); this is a discovery lead, not direct proof.

Function in CP: evidence, prediction, innovation

Gene function
Ryr1 encodes ryanodine receptor type 1, a homotetrameric calcium-release channel of the endoplasmic and sarcoplasmic reticulum. In skeletal muscle it is gated mechanically by the Cav1.1 voltage sensor; elsewhere it mediates calcium-induced calcium release, amplifying calcium entry and shaping cytosolic and nuclear signals. RYR1 mutations cause malignant hyperthermia; dantrolene is its clinical inhibitor.
Region function
The caudoputamen is the dorsal striatum, where direct- and indirect-pathway spiny projection neurons plus cholinergic and parvalbumin interneurons implement action selection, habit learning and dopamine-dependent reinforcement.
Published in this region
expression only No CP study resolves the Ryr1 isoform specifically. Ryanodine-receptor immunoreactivity occurs in striatal spiny neurons and, unlike IP3 receptors, also in cholinergic and parvalbumin interneurons (Martone 1997), and Mandikian et al. 2014 found RyR clusters juxtaposed to plasma-membrane Kv2.1 clusters most prominently in indirect-pathway spiny neurons; Allen ISH gives moderate Ryr1 signal in CP (energy 7.3-9.9).
Predicted function
Prediction: Ryr1-mediated calcium-induced calcium release in caudoputamen neurons should amplify depolarisation- and mGluR-evoked calcium at subsurface cisternae, feeding adjacent Kv2.1 and calcium-activated potassium channels and tuning afterhyperpolarisation and CREB-dependent plasticity. Striatal Ryr1 knockdown or local dantrolene is predicted to shrink the slow AHP, increase burst firing in indirect-pathway cells and impair habit learning.
Innovation
★★★★☆ 4/5 Almost all neuronal ryanodine-receptor work targets RyR2 and RyR3, leaving Ryr1 in striatum untested despite clear ISH expression and an approved blocker.
Tools
Dantrolene (RyR1-preferring, brain-penetrant), ryanodine and caffeine as probes; Ryr1 knockout and malignant-hyperthermia knock-in lines from the muscle field; isoform-specific anti-RyR1 antibodies; AAV-CRISPR knockdown with Drd2-Cre or Adora2a-Cre.
References

Direct evidence located at the region

Ryr1 Allen ISH at the CCF centroid of CP

Allen ISH experiment 71247657, section image 71093069 (section 322): the section that contains the CCF centroid of Caudoputamen 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
CP MERFISH region locator
Real single-cell MERFISH coordinates for the CP (Caudoputamen) 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

Ryr1 regional expression profile

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

Spatial profile

CP
2.57
OT
2.31
ACB
2.09
DG-po
1.76
CEAc
1.57
ILA2/3
1.55
DG-sg
1.44
ACAv2/3
1.35
TEa2/3
1.31
PL2/3
1.28
FC
1.28
ORBm2/3
1.26
CA2sp
1.24
ECT2/3
1.22
AUDv2/3
1.19
CEAl
1.19
IA
1.15
GU2/3
1.14
BLAp
1.12
AId2/3
1.11

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.278
Top-region fraction
0.044
Filter status
PASS

Interpretation limits