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Carleigh Studtmann's Dissertation Defense (2/10/2022): Diverse Mechanisms Impair Thalamic Circuit Function in a Dravet Syndrome Mouse Model

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Carleigh Studtmann

Dissertation Defense: Diverse mechanisms impair thalamic circuit function in a Dravet syndrome mouse model

Carleigh Studtmann

Graduate Student, Virginia Tech Translational Biology, Medicine, and Health
Graduate Research Assistant, Swanger Lab, Fralin Biomedical Research Institute at VTC
February 10, 2022 at 11:00 a.m.
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About this Dissertation

Dravet syndrome (DS) is an infantile epileptic encephalopathy that is caused by loss-of-function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel, NaV1.1. Haploinsufficiency of NaV1.1 in DS patients leads to imbalanced excitability across brain circuits, resulting in a broad phenotypic profile including drug-resistant convulsive and non-convulsive (absence) seizures, cognitive impairment, ataxia, and sleep disruption. Dysfunction in the somatosensory corticothalamic (CT) circuit underlies several DS phenotypes including absence seizures and sleep disturbances. Yet, the precise mechanisms underlying somatosensory CT circuit dysfunction in DS remain unclear. Here, Studtmann, working in the Swanger Lab, sought to identify the cellular and synaptic mechanisms underlying somatosensory CT circuit dysfunction in a haploinsufficiency DS mouse model, with the goal of revealing therapeutic targets by which to correct circuit function. This work reveals that NaV1.1 haploinsufficiency leads to cell-type-specific changes in the excitability of reticular thalamic (nRT), ventral posterolateral (VPL), and ventral posteromedial (VPM) neurons. Further, Studtmann and the lab identified alterations in both glutamatergic and GABAergic synaptic connectivity within the somatosensory CT circuit in DS mice. These findings introduce glutamatergic neuron dysfunction and synaptic alterations as novel disease mechanisms underlying thalamic circuit dysfunction in DS, providing new targets for therapeutic intervention. In addition, the research reveals that VPL and VPM neurons exhibit distinct firing properties in a healthy CT circuit, suggesting they differentially contribute to circuit-wide function in health and dysfunction in disease.

More About the Candidate and Project

Education

Virginia Tech Translational Biology, Medicine, and Health, Ph.D. Candidate

Bridgewater College, B.S., Biochemistry

Training

Graduate Research Assistant, Swanger Lab and Center for Neurobiology Research

 

Mentor

Sharon Swanger, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC

Committee Members

  • Steven Poelzing, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC and Co-Director, Translational Biology, Medicine, and Health Graduate Program, Virginia Tech
  • Konark Mukherjee, Ph.D., MBBS, Assistant Professor, Fralin Biomedical Research Institute at VTC
  • Michelle Olsen, Ph.D., Associate Professor and Director of Graduate Studies, School of Neuroscience, College of Science, Virginia Tech
  • Mark Witcher, M.D., Ph.D., Assistant Professor, Virginia Tech Carilion School of Medicine and Neurosurgery Specialist, Carilion Clinic

Honors

Research America Civic Engagement Microgrant Recipient (2019)

Virginia Community College Chancellor's Graduate Student Teaching Fellowship (2020) 

Presentations

Studtmann C and Swanger SA. Cellular and Synaptic Thalamic Alterations in a Dravet Syndrome Mouse Model. Poster presented at: The Central Virginia Chapter of SfN Annual Symposium; 2021 March 26-27; Virtual Meeting. 

Studtmann C, Topolski M, Safari M, Swanger SA. Cellular and Synaptic Thalamic Alterations in a Dravet Syndrome Mouse Model. Poster presented at: American Society for Neurochemistry Annual Meeting; 2021 June 28-July1; Virtual Meeting. 

Studtmann C, Topolski M, Safari M, Swanger SA. Intrinsic and synaptic mechanisms alter thalamic neuron function in a Dravet syndrome mouse model. Poster presented at: The Society for Neuroscience Annual Meeting; 2021 November 13-16; Virtual Meeting.

Publications

Studtmann, C., Ladislav, M., Topolski, M.A., Safari, M., and Swanger, S.A. (2021) NaV1.1 haploinsufficiency impairs glutamatergic and GABAergic neuron function in the thalamus. In revision. 

Studtmann, C., Topolski, M.A., and Swanger, S.A. (2022) Ventral posterolateral and Ventral posteromedial Thalamic Nuclei Exhibit Distinct Cellular Excitability. In preparation. 

Ladislav, M., Chen, Y., Topolski, M.A., Studtmann, C., Michniak, J., Gilmore, B., Swanger, S.A. NMDA receptor diversity enables cell-type-specific tuning of thalamic function. In preparation.

Studtmann, C. , LaConte, L. E. and Mukherjee, K. (2019), Comments on: A de novo in‐frame deletion of CASK gene causes early onset infantile spasms and supratentorial cerebral malformation in a female patient. Am J Med Genet, 179: 2514-2516. doi:10.1002/ajmg.a.61358

  • Science Outreach Coordinator - Virginia Tech Carilion Student Outreach Program (2019)
  • Communications Director, Big Lick of Science Podcast (2019)
  • Health and Wellness Chair, Roanoke Graduate Student Association (2019)
  • Judge for the Western Virginia Regional Science and Engineering Fair (2019, 2020)
  • STEAM Day Exhibit at Taubman Museum of Art (2019)
  • Career Day at East Salem Elementary School (2019)