Focal impaired awareness seizures in a rodent model: A functional anatomy

Objective Patients with temporal lobe epilepsy (TLE) frequently report debilitating comorbidities such as memory impairments, anxiety, and depression. An extensive neuronal network generates epileptic seizures and associated comorbidities, but a detailed description of this network is unavailable, which requires the generation of neuronal activation maps in experimental animals. Methods We recorded electrographic seizures from the hippocampi during a kindling-evoked focal impaired awareness seizure with observed freezing, facial twitching, and involuntary head bobbing. We mapped seizure circuits activated during these seizures by permanently tagging neurons through activity-induced immediate early genes, combined with immunohistochemical approaches. Results There was bilateral activation of circuits necessary for memory consolidation, including the hippocampal complex, entorhinal cortex, cingulate gyrus, retrosplenial cortex, piriform cortex, and septohippocampal complex in kindled animals compared with unstimulated awake behaving mice. Neuronal circuits in the ventral hippocampus, amygdala, and anterior cingulate cortex, which regulate the stress response of hypothalamic-pituitary-adrenal axis, were also markedly activated during a focal impaired awareness seizure. Significance This study highlights neuronal circuits preferentially activated during a focal awareness impaired seizure in a rodent model. Many of the seizure-activated neuronal circuits are critical modulators of memory consolidation and long-term stress/depression response. The hijack of these memory and depression regulatory systems by a focal seizure could account for the frequent reports of comorbidities such as memory impairment and depression in many TLE patients.