Epilepsy is a common problem with the temporal lobe being a frequent site of seizure onset. There are numerous changes that occur in the temporal lobe that accompany the onset of seizures including loss of neurons, changes in synaptic connections, alterations in neurotransmitter receptors and birth of new neurons. This study will address the role of neurogenesis in the epileptic process by examining how the birth of new neurons affects both the types of neurotransmitter receptors expressed and the rate of spontaneous seizure development. The studies will be carried out in a rat model of temporal lobe epilepsy and in surgical tissue removed from children with refractory epilepsy. Neurons from thin slices of the temporal lobe will be identified as newly born or mature and individually isolated. The neurotransmitter receptors that each neuron expresses will be analyzed to determine if the newly born neurons, the mature neurons or both, are changing their expression pattern with the formation of epilepsy. We hope that this will shed light on what changes occur in neurotransmitter receptors and which neurons are responsible for the epilepsy-associated changes. We will directly assess the role of newborn neurons in the development of temporal lobe epilepsy. We will block neurogenesis after an episode of prolonged seizure and measure the number of animals that develop epilepsy to determine if neurogenesis is pro or anti-epileptic. Our hope is that by understanding the changes in neurotransmitter expression and the role of neurogenesis in the formation of an epileptic focus, we will identify specific targets to attack and prevent the development of epilepsy. The K08 Award mechanism will allow me to undertake mentored research training in pediatric epilepsy. The studies proposed will take place in the laboratories of Drs. Douglas Coulter and Amy Brooks-Kayal, at The Children's Hospital of Philadelphia. This Award will facilitate my goal of a career in academic medicine.
