Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0013421 (
dystonia
)
8,418
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The type 1 inositol 1,4,5- trisphosphate receptor (
IP3R1
) is a Ca(2+) channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking
IP3R1
show seizure-like behavior; however the cellular and neural circuit mechanism by which
IP3R1
deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking
IP3R1
specifically in the cerebellum and brainstem experience
dystonia
and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific
dystonic movements
. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate
IP3R1
-dependent PC firing patterns in cerebellum in motor coordination and the expression of
dystonia
through the olivo-cerebellar pathway.
...
PMID:IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. 2410 34
