Role of Midline Thalamic Circuits in Limbic Seizures

The midline thalamus has been shown to have a critical role in limbic seizures. The presumed reason for its importance has been its widespread excitatory connectivity with the limbic network. However, the physiological relationship of the midline thalamus with respect to the network, and the ways in which that relationship contributes to seizure initiation and spread, are unclear. This thesis explores the relationship between the midline thalamus and the limbic network in animal models of limbic seizures. This includes: (1) an examination of signaling of the midline thalamus to the prefrontal cortex in rats with kindled or spontaneous limbic seizures, and how that signaling changes as the chronic model develops, (2) an examination of divergent-convergent circuits formed between the thalamus and two separate limbic pathways: the subiculum-prefrontal cortex and the entorhinal cortex-piriform cortex pathways, and how theses circuits may influence seizure spread, (3) an examination of how GABAergic modulation of thalamic neurons can have a widespread effect on limbic circuits, such as the subiculum-prefrontal cortex pathway. The conclusion of this thesis is that the role of the midline thalamus in limbic seizures can be derived, in part, from its extensive physiological influence on signaling within the limbic network. This work reinforces the evidence that the midline thalamus may make an effective clinical target for patients with mesial temporal lobe epilepsy. It also provides evidence that the role of the midline thalamus in the normal functional processes of the limbic network merit further exploration.

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