ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Postnatal loss of P/Q-type channels confined to rhombic-lip-derived neurons alters synaptic transmission at the parallel fiber to purkinje cell synapse and replicates genomic Cacna1a mutation phenotype of ataxia and seizures in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 53 citations in OpenAlex.
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- Spatial genomics of AAV vectors reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo.Nature biotechnology · 2026Article
- Cerebellar α1Cellular and molecular life sciences : CMLS · 2025Article
- Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Intrafamilial neurological phenotypic variability due to either biallelic or monoallelic pathogenic variants inFrontiers in neurology · 2024Article
- Controlling absence seizures from the cerebellar nuclei via activation of the GCellular and molecular life sciences : CMLS · 2022Article
- Reversing frontal disinhibition rescues behavioural deficits in models of CACNA1A-associated neurodevelopment disorders.Molecular psychiatry · 2021Article
- A stable proportion of Purkinje cell inputs from parallel fibers are silent during cerebellar maturation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cognitive deficits in episodic ataxia type 2 mouse models.Human molecular genetics · 2021Article
- The cerebellum and epilepsy.Epilepsy & behavior : E&B · 2021Review
- Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks.Nature communications · 2021Article
- Response of Voltage-Gated Sodium and Calcium Channels Subtypes on Dehydroepiandrosterone Treatment in Iron-Induced Epilepsy.Cellular and molecular neurobiology · 2021Article
- Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) as a Novel Regulator of Early Astroglial Differentiation.Frontiers in cellular neuroscience · 2021Article
- Selective loss of the GABAJournal of neurophysiology · 2020Article
- Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2.Biomedicines · 2020Review
- Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias.International journal of molecular sciences · 2020Review
- Epilepsy and brain channelopathies from infancy to adulthood.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid.Science translational medicine · 2020Article
- RGS2 drives male aggression in mice via the serotonergic system.Communications biology · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Ataxia, episodic dyskinesia, and thalamocortical seizures are associated with an inherited loss of P/Q-type voltage-gated Ca(2+) channel function. P/Q-type channels are widely expressed throughout the neuraxis, obscuring identification of the critical networks underlying these complex neurological disorders. We showed recently that the conditional postnatal loss of P/Q-type channels in cerebellar Purkinje cells (PCs) in mice (purky) leads to these aberrant phenotypes, suggesting that intrinsic alteration in PC output is a sufficient pathogenic factor for disease initiation. The question arises whether P/Q-type channel deletion confined to a single upstream cerebellar synapse might induce the pathophysiological abnormality of genomically inherited P/Q-type channel disorders. PCs integrate two excitatory inputs, climbing fibers from inferior olive and parallel fibers (PFs) from granule cells (GCs) that receive mossy fiber (MF) input derived from precerebellar nuclei. In this study, we introduce a new mouse model with a selective knock-out of P/Q-type channels in rhombic-lip-derived neurons including the PF and MF pathways (quirky). We found that in quirky mice, PF-PC synaptic transmission is reduced during low-frequency stimulation. Using focal light stimulation of GCs that express optogenetic light-sensitive channels, channelrhodopsin-2, we found that modulation of PC firing via GC input is reduced in quirky mice. Phenotypic analysis revealed that quirky mice display ataxia, dyskinesia, and absence epilepsy. These results suggest that developmental alteration of patterned input confined to only one of the main afferent cerebellar excitatory synaptic pathways has a significant role in generating the neurological phenotype associated with the global genomic loss of P/Q-type channel function.
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