One in 26 people experience epilepsy at some point in their life and temporal lobe epilepsy is the most common
adult focal epilepsy. New and innovative therapies are required to treat the many cases of temporal lobe epilepsy
that are poorly controlled with conventional medications. Ideally, treatments should be based on a detailed
understanding of the mechanisms that give rise to seizures, but these biological mechanisms are poorly
understood. The conventional approach is to surgically remove the seizure “focus” in attempts to alleviate
seizures, but identifying the focus is challenging. Even in cases when the focus is ostensibly clear, surgery may
not prevent seizures. An alternative hypothesis is that even classically focal epilepsies, such as temporal lobe
epilepsy, rely on more distributed brain networks. One such network that is well-positioned to support seizures
is the Papez circuit, which embeds the hippocampus, a classic seizure focus, in a recurrent excitatory network.
Preliminary work demonstrates that the medial mammillary body, the hypothalamic node of this circuit, drives
synchronous network events in the hippocampus and highlights a potential role as an external controller for
pathologically synchronous states (i.e., epileptiform events). Using transgenic mouse lines and cell-type-specific
tools, two divergent pathways from the medial mammillary body will be investigated to determine 1) how seizure
activity spreads through these pathways, 2) whether these pathways are necessary and sufficient for seizure
activity, and 3) if targeted, non-invasive neuromodulation with ultrasound can control seizure activity. Completing
this grant will advance our understanding of the mechanisms that generate seizure activity and take a first step
towards translation using a clinically relevant treatment modality. The candidate's long-term goal is to establish
an independent research program that sheds light on the organization and function of networks that support
physiological processes (e.g., memory) and pathological seizures. To attain this goal, the candidate has outlined
a comprehensive, personalized program that identifies plans for career development in research training,
neuroscience knowledge, technique development, grantsmanship, scientific management, and others. This
training plan outlines a pathway to independence (i.e., from postdoc to establishing their own laboratory) that
has a realistic timeline and is supported excellent resources at Stanford University, collaboration, and an
established mentor with extensive experience relevant to this goal.