BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:Blue Brain Seminar - Building and deconstructing epilepsy circuits using mice and human brain organoids DTSTART:20191216T150000 DTEND:20191216T160000 DTSTAMP:20260414T145259Z UID:5fe7805943d0e5b311e2887d5b3102b3e084ddb4996a45f6807e1b33 CATEGORIES:Conferences - Seminars DESCRIPTION:Christopher D. Makinson\nBlue Brain is delighted to announce t hat the next seminar in the series in Neural Computation\, will be on ‘B uilding and deconstructing epilepsy circuits using mice and human brain or ganoids’. The seminar will be given by Christopher D. Makinson\, Ph.D.\, Postdoctoral Research Fellow Huguenard and Pasca Laboratories\, Stanford University.\n\nAbstract:\nEpileptic seizures represent abrupt switches in brain state that often arise from a background of normal activity to inter rupt ongoing processes before terminating just as quickly. Understanding h ow these events are generated and maintained is an important clinical and basic goal. Using mice carrying a mutation in the voltage-gated sodium cha nnel Nav1.6 (Scn8a) as a model of absence epilepsy\, we show how seizures can be caused by a breakdown in synaptic inhibition within a specific path way of a rhythm-generating circuit within the thalamus. This pathway\, we propose\, represents an endogenous seizure suppressing component of the th alamocortical circuit that may also constrain synchronous features of phys iological rhythms. Interestingly\, while conducive of absence seizures via increased thalamic excitability\, these Scn8a mutations also effectively suppress cortically-driven convulsive seizures. We find that Scn8a-depende nt cortical seizure suppression arises via two co-conspiring factors\, red uced excitatory neuron output and reduced disinhibition (i.e. reduced inhi bition of inhibitory cells).\nLastly\, I will share with you our recent ef forts to understand epilepsy pathogenesis using a novel 3D human cell cult ure model of the developing cortex that is generated from induced pluripot ent stem cells. Using this system\, we find that an epilepsy mutation in t he L-type calcium channel Cav1.2 (CACNA1C) alters the formation of cortica l networks\, in part\, by impairing the migratory behavior and excitabilit y of integrating inhibitory cells.\nTogether these results demonstrate tha t the origins of some epilepsies can be traced back to the very earliest p hases of circuit assembly\, often before seizures or other overt aspects o f the disorder are apparent and highlight the need to continue to advance new methods to understand brain development and function.\n\nBio:\nChristo pher Makinson\, PhD\, is a research fellow in the Department of Neurology at Stanford University working under the mentorship of Drs John Huguenard and Sergiu Pasca. His research focuses on understanding the role of ion-ch annels in development and neurological diseases such as epilepsy using rod ent and human brain organoid models.\nDuring his postdoc with Dr John Hugu enard\, Dr Makinson studied how mutations in ion-channels cause absence ep ilepsy. These studies provided insight into how the thalamus controls netw ork synchrony and identified a novel mechanism of seizure generation. Dr M akinson also worked with Dr Sergiu Pasca to develop some of the first huma n induced pluripotent stem cell-derived brain organoids.\nNext year Dr. Ma kinson will join the faculty of the departments of Neurology and Neuroscie nce at Columbia University where he will continue to study the role of ion -channels in early development. LOCATION:B1 6 272.043 https://plan.epfl.ch/?room==B1%206%20272.043 STATUS:CONFIRMED END:VEVENT END:VCALENDAR