Progression to seizure susceptibility with age in Alpha-1A knockout mice characterized by c-Fos expression
Epilepsy is a seizure disorder that affects 3.4 million people in the US alone. This thesis studies the progression to spontaneous motor seizures in alpha-1A knockout mice to give better insight on the interactions between alpha-1A receptor dysfunction and the development of motor seizures with age. This is relevant to the study of temporal lobe epilepsy as similar brain areas such as the amygdala, hippocampus, and piriform cortex are involved in seizure activity in both humans and rodents. As alpha-1A receptors are present mainly on GABAergic inhibitory interneurons and a knockout affects inhibitory transmission in the brain, the excitatory/inhibitory imbalance associated with development of epilepsy is also relevant. A behavioral analysis of motor seizure behaviors was conducted using a modified Racine Scale followed by a cardiac perfusion. Immunohistochemistry for c-Fos was also performed to establish active brain regions associated with seizure activity. Based on analysis of seizure behaviors and associated Racine scores, it was concluded that spontaneous seizures in ARa1AKO mice begin around the 5.75 to 6-month mark. Cell count data suggests that a higher Racine score relates to a higher level of c-Fos expression in several regions of interest including the amygdala, dentate gyrus, hypothalamus, and piriform cortex. It is also suggested that the path of seizure progression in alpha-1A knockout mice begins in the thalamus.