Abstracts

Rationale: Childhood Absence Epilepsy (CAE) is the most common pediatric epilepsy. A striking feature of CAE is the unassailable ability to trigger seizures by hyperventilation. The mechanism(s) underlying hyperventilation-induced seizures is unknown. However, insight into hyperventilation-induced absence seizures will lead to more efficacious treatments than the current, ill-favored anti-epilepsy drugs. Methods: All experiments were conducted using the rodent model of absence epilepsy, the WAG/Rij rat.  Combined plethysmography and EEG experiments demonstrate that hyperventilation-induced seizures are found in the WAG/Rij rat.  To assess midline thalamic activation after hyperventilation, we peformed immunohistochemistry and in situ hybridization to demonstrate expression of the immediate early gene c-Fos in the midline thalamus.   Results: Our immunohistochemistry (n= 5) and in situ (n=5) data reveal c-Fos expression in the midline thalaus after exposure to 30min of hypoxia to induce hyperventilation.  Conclusions: Identification of c-fos­ ­­positive cells in the midline thalamus is a novel finding and provides us a first glance into understanding how hyperventilation modulates thalamocortical activity to produce absence seizures. Long-standing evidence demonstrates that the midline thalamus has diffuse projections throughout the cortex, as well as reciprocal connectivity with the reticular thalamic nucleus (RT).  Additionally, our c-fos­ data highlights an active population of midline cells during hypoxia-induced seizures. We hypothesize that the midline exerts a strong modulatory tone within intrathalamic and thalamocortical circuits. Future experiments aim to address how midline activation affects spike-and-wave discharge (SWD) activity as well as midling connectivity with RT. Funding: NIGMS T32Gm007055