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Type 1 inositol trisphosphate receptor regulates cerebellar circuits by maintaining the spine morphology of purkinje cells in adult mice.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2013 Jul 24; Vol. 33 (30), pp. 12186-96. - Publication Year :
- 2013
-
Abstract
- The structural maintenance of neural circuits is critical for higher brain functions in adulthood. Although several molecules have been identified as regulators for spine maintenance in hippocampal and cortical neurons, it is poorly understood how Purkinje cell (PC) spines are maintained in the mature cerebellum. Here we show that the calcium channel type 1 inositol trisphosphate receptor (IP3R1) in PCs plays a crucial role in controlling the maintenance of parallel fiber (PF)-PC synaptic circuits in the mature cerebellum in vivo. Significantly, adult mice lacking IP3R1 specifically in PCs (L7-Cre;Itpr1(flox/flox)) showed dramatic increase in spine density and spine length of PCs, despite having normal spines during development. In addition, the abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused unexpectedly severe ataxia in adult L7-Cre;Itpr1(flox/flox) mice. Our findings reveal a specific role for IP3R1 in PCs not only as an intracellular mediator of cerebellar synaptic plasticity induction, but also as a critical regulator of PF-PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism may underlie motor coordination and learning in adults.
- Subjects :
- Animals
Cerebellar Ataxia genetics
Cerebellar Ataxia pathology
Cerebellum cytology
Cerebellum pathology
Chimera
Dendritic Spines pathology
Female
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Mutant Strains
Neuronal Plasticity physiology
Nystagmus, Optokinetic physiology
Purkinje Cells cytology
Purkinje Cells ultrastructure
Reflex, Vestibulo-Ocular physiology
Synapses physiology
Cerebellar Ataxia physiopathology
Cerebellum physiology
Dendritic Spines physiology
Inositol 1,4,5-Trisphosphate Receptors genetics
Inositol 1,4,5-Trisphosphate Receptors metabolism
Purkinje Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 33
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 23884927
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.0545-13.2013