BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:Building and deconstructing epilepsy circuits using mice and human
  brain organoids
DTSTART:20191216T150000
DTEND:20191216T160000
DTSTAMP:20260408T034938Z
UID:c524fa96cb9fb9f3bcf43835d5f92b657ba05ad4629a16b50383f8c7
CATEGORIES:Conferences - Seminars
DESCRIPTION:Christopher Makinson\, PhD\, Department of Neurology\, Stanfor
 d University\nEpileptic seizures represent abrupt switches in brain state 
 that often arise from a background of normal activity to interrupt ongoing
  processes before terminating just as quickly. Understanding how these eve
 nts are generated and maintained is an important clinical and basic goal. 
 Using mice carrying a mutation in the voltage-gated sodium channel Nav1.6 
 (Scn8a) as a model of absence epilepsy\, we show how seizures can be cause
 d by a breakdown in synaptic inhibition within a specific pathway of a rhy
 thm-generating circuit within the thalamus. This pathway\, we propose\, re
 presents an endogenous seizure suppressing component of the thalamocortica
 l circuit that may also constrain synchronous features of physiological rh
 ythms. Interestingly\, while conducive of absence seizures via increased t
 halamic excitability\, these Scn8a mutations also effectively suppress cor
 tically-driven convulsive seizures. We find that Scn8a-dependent cortical 
 seizure suppression arises via two co-conspiring factors\, reduced excitat
 ory neuron output and reduced disinhibition (i.e. reduced inhibition of in
 hibitory cells).\nLastly\, I will share with you our recent efforts to und
 erstand epilepsy pathogenesis using a novel 3D human cell culture model of
  the developing cortex that is generated from induced pluripotent stem cel
 ls. Using this system\, we find that an epilepsy mutation in the L-type ca
 lcium channel Cav1.2 (CACNA1C) alters the formation of cortical networks\,
  in part\, by impairing the migratory behavior and excitability of integra
 ting inhibitory cells.\nTogether these results demonstrate that the origin
 s of some epilepsies can be traced back to the very earliest phases of cir
 cuit assembly\, often before seizures or other overt aspects of the disord
 er are apparent and highlight the need to continue to advance new methods 
 to understand brain development and function.\n\nChristopher Makinson\, Ph
 D\, is a research fellow in the Department of Neurology at Stanford Univer
 sity working under the mentorship of Drs John Huguenard and Sergiu Pasca. 
 His research focuses on understanding the role of ion-channels in developm
 ent and neurological diseases such as epilepsy using rodent and human brai
 n organoid models.\nDuring his postdoc with Dr John Huguenard\, Dr Makinso
 n studied how mutations in ion-channels cause absence epilepsy. These stud
 ies provided insight into how the thalamus controls network synchrony and 
 identified a novel mechanism of seizure generation. Dr Makinson also worke
 d with Dr Sergiu Pasca to develop some of the first human induced pluripot
 ent stem cell-derived brain organoids.\nNext year Dr. Makinson will join t
 he faculty of the departments of Neurology and Neuroscience at Columbia Un
 iversity 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