Thesis Format
Integrated Article
Degree
Master of Science
Program
Neuroscience
Supervisor
Poulter, Michael O.
2nd Supervisor
Martinez-Trujillo, Julio
Co-Supervisor
Abstract
Traumatic Brain Injury (TBI) often leads to the development of epilepsy, especially with the occurrence of stressful events. Stressors increase the levels of corticotropin-releasing factor (CRF) in the amygdala, which can be damaged by the secondary effects of TBI. It is hypothesized that the activity of CRF receptor type 1 (CRFR1) in the amygdala is altered post-TBI and supports the generation of epileptiform waves, namely high-frequency oscillations (HFOs). Sprague-Dawley rats were given a moderate TBI and in vivo recordings of the amygdala were taken during the administration of an acute tail pinch stressor. The stressor increased broadband activity which included the occurrence of HFOs. Moreover, HFO amplitudes were found to be coupled to the phase of a simultaneous theta wave (4 – 8Hz). Furthermore, application of a CRFR1 antagonist disrupted the generation of HFOs and their phase-amplitude coupling with theta, and these effects were reverted after washout of the antagonist.
Summary for Lay Audience
Traumatic brain injury (TBI) causes lasting changes which make the brain susceptible to developing epilepsy. Stressful events that occur after TBI often trigger the occurrence of seizures and increase the likelihood that the brain will become epileptic. The exact interaction between the effects of TBI and stress that leads to epilepsy is unclear and needs investigation. It is known that the amygdala, a small region of the brain that plays a key role in processing stress, is often damaged due to the effects of TBI. Therefore, this phenomenon can be studied by measuring the activity of the amygdala that has been affected by TBI and stress. We can simulate these effects and measure the outcome using an animal model. For the experiments in this thesis, Sprague-Dawley rats were given a moderate TBI via a surgical process and a recording electrode was implanted in the amygdala of each rat. The brain-injured rats were stressed for short periods of time by applying a stressor called the tail pinch. Recordings of the amygdala during stress revealed the occurrence of high-frequency oscillations (HFOs), which are brainwaves that are implicated in the development of epilepsy. Furthermore, these HFOs were found to be interacting with another simultaneously occurring brainwave called the theta oscillation, which seemed to be acting like a pacemaker for the HFOs. This peculiarity, called phase-amplitude coupling, may be a contributing mechanism to the interaction between TBI and stress that leads to epilepsy.
Recommended Citation
Jung, Paul, "High Frequency Oscillations are Phase-Amplitude Coupled in Stress Induced Seizures Following Traumatic Brain Injury" (2019). Electronic Thesis and Dissertation Repository. 6626.
https://ir.lib.uwo.ca/etd/6626