Dissertation
The roles of L-type calcium channels in behavior and cerebellar structure
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2024
DOI: 10.25820/etd.007376
Abstract
Mutations in L-type calcium channels have been associated with neuropsychiatric disorders like autism spectrum disorder, schizophrenia, and bipolar disorder. Recent work in mice has found that global knockout of the L-type calcium channels CaV1.2 and CaV1.3 each result in social, motor, and cognitive impairments; however, it is unclear how a loss of CaV1 channels leads to behavioral impairments. The goal of this work is to use multiple conditional knockout mouse models to understand the specific roles of CaV1.2, CaV1.3 and α2δ-4 in the brain. From this work, we established that a global knockout of the L-type channel subunit α2δ-4 is sufficient to cause impairments in cognitive and motor behaviors. We established that a neuron-specific knockout of CaV1.2 is sufficient to cause impairments in cognitive, motor, and social behaviors. We found that a global knockout of CaV1.3 does not alter most measures of cerebellar cortex morphology but does result in less complexity in the dendrites of Purkinje cells, the primary output neuron of the cerebellar cortex. Finally, we established that a conditional deletion of CaV1.3 from ~25% of cerebellar molecular layer interneurons is sufficient to impair motor learning behaviors. Together, this work contributes to our understanding of the complex role L-type channels play in the brain. Given the genetic links between L-type channels and neuropsychiatric disorders, a better understanding of the role of L-type channels in neuronal function may contribute to our understanding of neuropsychiatric disorders.
Details
- Title: Subtitle
- The roles of L-type calcium channels in behavior and cerebellar structure
- Creators
- Annette Klomp
- Contributors
- Aislinn Williams (Advisor)John Freeman (Committee Member)Carl Andrew Frank (Committee Member)Gordon Buchanan (Committee Member)Sheila Baker (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Spring 2024
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007376
- Number of pages
- xviii, 174 pages
- Copyright
- Copyright 2024 Annette Klomp
- Grant note
- Chapter 2 was supported by grants from the National Institutes of Health: R03NS115653 and R01EY026817 to AL; NS075599 to AFR; MH116043 to NN; NS113189 to YMU; DC002842, DC012049, and DC017955 to RJS. Chapters 3-5 were funded by KL2TR002536 (Aislinn J. Williams), the Roy J. Carver Charitable Trust (Aislinn J. Williams), NINDS T32NS007124 (Annette J. Klomp, Ashley Plumb), the Summer Undergraduate Research Program at the University of Iowa (Jacqueline B. Mehr), the Biomedical Scholars Summer Undergraduate Research Program (Martha Pace), T32MH019113 (Deniz A. Madencioglu), and the iDREAM Program (Maria Fernanda Hermosillo Arrieta). This work utilized the Leica LMD7000 in the University of Iowa Central Microscopy Research Facilities that was purchased with funding from the NIH SIG grant 1 S10 OD016316-01. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. (ii)
- Language
- English
- Date submitted
- 04/15/2024
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (page 133-169).
- Public Abstract (ETD)
L-type voltage gated calcium channels are pores in the cell membrane that open when the cell gets depolarized. I study how these channels regulate brain structure and behavior. The L-type channel subunits Cacna1d, Cacna1c, and Cacna2d4 are risk genes for psychiatric disorders including autism spectrum disorder, schizophrenia, and bipolar disorder. The goal of my work is to understand the normal functions of L-type channels and by doing so I hope to broaden our understanding of how disruptions in these genes contribute to psychiatric disorders.
- Academic Unit
- Interdisciplinary Studies Program
- Record Identifier
- 9984647648002771
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