Authors :
Presenting Author: Maria-Belen Perez-Ramirez, PhD – Stanford University
Juliet Knowles, M.D., PhD. – Neurology – Stanford University; Isabel Parada, PhD – Neurology – Stanford University; David Prince, PhD – Stanford University
Rationale: In human and animal models, an increase in the immune response has been reported following status epilepticus (SE). SE is a life-threatening emergency with chronic neurological consequences. Prolonged neocortical seizures can induce microglia activation and injury to long-distance interconnected structures, such as the thalamus, that might contribute to sequelae of focal SE (FSE). We hypothesized that intense cortical output during FSE Induced in somatosensory cortex (SS ctx) would activate the immune response to induce structural and functional changes in excitatory connectivity within SS ctx and its downstream targets in thalamus (nRT and VB). The increases in microgliosis, astrocytosis, and enhanced excitatory connectivity would result in alterations in thalamocortical circuit function.
Methods: With epidural application of gabazine and 4-AP (150µM each), we induced FSE over the somatosensory cortex of anesthetized mice. Ten days later, we obtained confocal images of SS ctx, medial nRt, and VB sections immunostained for pre- and postsynaptic markers of excitatory synapses. Counts of Iba1-CD68-IR microglia and GFAP-IR astrocytes within ROIs were analyzed from non-overlapping confocal sections. Whole-cell voltage-clamp recordings in SS ctx, nRT, and VB neurons were used to measure sEPSC frequency. In vitro local field potentials were obtained from SS ctx to calculate the incidence of bursting slices. Statistical significance was tested with Wilcoxon test with a p< 0.05.