Our initial grant funding focused on the earliest period following experimentally-induced seizures.
We documented robust physical interactions between microglia and neurons in epileptic contexts and
concluded that microglia provide beneficial functions in the acute seizures. In this renewal, we will
further investigate microglial activities in the epileptic brain in vivo and combine cellular and functional
imaging with electrophysiological and behavioral studies in experimental mouse seizure models. We
will extend our findings from the initial funding cycle to further characterize microglial activities in the
epileptic brain following seizures and provide further evidence of microglial neuroprotection in the acute
phase of kainic acid (KA)-induced seizures. In addition, we will investigate microglial roles in the
epileptic brain in the chronic phase of epilepsy using microglial ablation and chemogenetic DREADD
approaches. Our central hypothesis is that microglia play opposing roles during the acute phase of
seizures and the chronic phase of epileptogenesis. This hypothesis will be tested along the following
In Aim 1, we will investigate the dynamics and function of seizure-induced microglial process pouches.
In Aim 2, we will determine microglial contributions to epileptogenesis. Finally, in Aim 3, we will
ascertain opposing microglial roles in acute seizures and chronic epilepsy using DREADD approaches.
When completed, this grant will extend the findings of the initial funding to elucidate the beneficial roles
for microglia in the acute phase of seizures Furthermore, this renewal will highlight detrimental
contributions by microglia in promoting seizure-induced neurogenesis, neuronal sprouting, neuronal
excitability and spontaneous seizures in the chronic phase of seizures. This study will not only improve
our understanding of microglial mechanism to epileptogenesis but also demonstrate that microglia are
potential therapeutic targets for the treatment seizures and epilepsy.