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Chronic effects of traumatic brain injury on the corticothalamic circuit

  • Author(s): Holden, Stephanie
  • Advisor(s): Swanson, Raymond
  • et al.
Abstract

Traumatic brain injury (TBI) affects 69 million people worldwide each year and is associated with many adverse health outcomes. But we still don’t fully understand which cells or circuits in the brain are chronically disrupted by TBI, or how to prevent or treat these outcomes. TBI-related health outcomes likely reflect secondary injuries that arise over the long term as consequences of the initial impact. In Chapters 2 and 3, we investigate the secondary injury processes that develop in the corticothalamic circuit, using a mouse model of mild injury that only directly injures the cortex. In Chapter 2, we identify which intrinsic, synaptic, and bulk cortical properties in the peri-injured cortex and the functionally connected thalamus are chronically altered by TBI, using electrophysiological recordings approaches. We also explore the role of the C1q complement pathway in TBI, and we find that blocking C1q reduces inflammation and neuronal loss in the corticothalamic circuit. In Chapter 3, we test the chronic effects of a novel small molecule therapeutic that reprograms astrocyte transcriptional states on outcomes such as inflammation and seizure susceptibility after TBI. In Chapter 4, we explore the fundamental properties of working memory, a cognitive function that involves the prefrontal cortex. Working memory is one of many cognitive functions known to be disrupted in TBI but before we study this function in the context of disease, we first dive into the basic intrinsic properties of neurons that underlie working memory. Studying the cellular and circuit mechanisms of both basic cognitive functions such as working memory and chronic disease processes such as TBI will help to identify new targets and therapeutic treatments for TBI-related health outcomes.

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