Deletion of the voltage-gated calcium channel gene, Ca V 1.3, reduces Purkinje cell dendritic complexity without altering cerebellar-mediated eyeblink conditioning

Annette J. Klomp; Martha Pace; Jacqueline B. Mehr; Maria Fernanda Hermosillo Arrieta; Cessily Hayes; Anthony Fleck; Shane Heiney; Aislinn J. Williams

doi:10.1101/2025.03.27.645586

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Deletion of the voltage-gated calcium channel gene, Ca V 1.3, reduces Purkinje cell dendritic complexity without altering cerebellar-mediated eyeblink conditioning

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Deletion of the voltage-gated calcium channel gene, Ca V 1.3, reduces Purkinje cell dendritic complexity without altering cerebellar-mediated eyeblink conditioning

Annette J. Klomp, Martha Pace, Jacqueline B. Mehr, Maria Fernanda Hermosillo Arrieta, Cessily Hayes, Anthony Fleck, Shane Heiney and Aislinn J. Williams

bioRxiv

Cold Spring Harbor Laboratory

03/29/2025

DOI: 10.1101/2025.03.27.645586

PMCID: PMC11974831

PMID: 40196480

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https://doi.org/10.1101/2025.03.27.645586View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Genetic variation in CACNA1D, the gene that encodes the pore-forming subunit of the L-type calcium channel CaV1.3, has been associated with increased risk for neuropsychiatric disorders that display abnormalities in cerebellar structures. We sought to clarify if deletion of CaV1.3 in mice would induce abnormalities in cerebellar cortex cytoarchitecture or synapse morphology. Since CaV1.3 is highly expressed in cerebellar molecular layer interneurons (MLIs) and L-type channels appear to regulate GABA release from MLIs, we hypothesized that loss of CaV1.3 would alter GABAergic synapses between MLIs and Purkinje cells (PCs) without altering MLI numbers or PC structure. As expected, we did not observe changes in the numbers of MLIs or PCs. Surprisingly, CaV1.3 KO mice do have decreased complexity of PC dendritic arbors without differences in the number or structure of GABAergic synapses onto PCs. Loss of CaV1.3 was not associated with impaired acquisition of delay eyeblink conditioning. Therefore, our data suggest that CaV1.3 expression is important for PC structure but does not affect other measures of cerebellar cortex morphology or cerebellar function as assessed by delay eyeblink conditioning.

Details

Title: Subtitle: Deletion of the voltage-gated calcium channel gene, Ca V 1.3, reduces Purkinje cell dendritic complexity without altering cerebellar-mediated eyeblink conditioning
Creators: Annette J. Klomp - University of Iowa
Martha Pace - Upper Iowa University
Jacqueline B. Mehr - Robert Wood Johnson University Hospital
Maria Fernanda Hermosillo Arrieta - University of Iowa
Cessily Hayes - University of Iowa
Anthony Fleck - University of Iowa
Shane Heiney - University of Iowa
Aislinn J. Williams - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.03.27.645586
PMID: 40196480
PMCID: PMC11974831
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 03/29/2025
Academic Unit: Psychiatry; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984808531702771

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