Deletion of the Voltage-Gated Calcium Channel Gene, Ca V 1.3, Reduces Purkinje Cell Dendritic Complexity Without Altering Cerebellar-Mediated Eyeblink Conditioning

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

doi:10.1007/s12311-025-01914-y

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

Cerebellum (London, England), Vol.24(6), 164

10/11/2025

DOI: 10.1007/s12311-025-01914-y

PMCID: PMC12515208

PMID: 41075059

Appears in UI Libraries Support Open Access

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https://doi.org/10.1007/s12311-025-01914-yView

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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 density or PC structure. As expected, we did not observe changes in the density 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.

Animals

Calcium Channels, L-Type - deficiency

Calcium Channels, L-Type - genetics

Cerebellum - cytology

Cerebellum - physiology

Conditioning, Eyelid - physiology

Dendrites - physiology

Dendrites - ultrastructure

Interneurons

Male

Mice

Mice, Inbred C57BL

Mice, Knockout

Purkinje Cells - cytology

Purkinje Cells - physiology

Synapses

UIOWA OA Agreement

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 Klomp - University of Iowa
Martha Pace - Upper Iowa University
Jacqueline Mehr - Rutgers, The State University of New Jersey
Maria Fernanda Hermosillo Arrieta - Iowa Neuroscience Institute, Iowa City, IA, USA
Cessily Hayes - University of Iowa
Anthony Fleck - Iowa Neuroscience Institute, Iowa City, IA, USA
Shane Heiney - Iowa Neuroscience Institute, Iowa City, IA, USA
Aislinn Williams - University of Iowa
Resource Type: Journal article
Publication Details: Cerebellum (London, England), Vol.24(6), 164
DOI: 10.1007/s12311-025-01914-y
PMID: 41075059
PMCID: PMC12515208
NLM abbreviation: Cerebellum
ISSN: 1473-4222
eISSN: 1473-4230
Publisher: Springer Nature; NEW YORK
Grant note: KL2TR002536 / NIH HHS NS104836 / NIH HHS T32NS007124 / NIH HHS
Language: English
Date published: 10/11/2025
Academic Unit: Psychiatry; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9985014893502771

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