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X-WR-CALNAME:Max Heinrich Thesis Defense: Spontaneous activity in the mouse
  visual cortical slice: biophysical characterization and pathophysiology
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20261006T214221Z
UID:tag:localist.com\,2008:EventInstance_48276553182246
DTSTART:20241213T200000Z
DTEND:20241213T210000Z
DESCRIPTION:Max Heinrich – Thesis Defense\n\nDate/Time/Location: December
  13th at 3pm\n\nIn-person Locaton: Singleton Auditorium 46-3002\n\nOn Zoom
 : https://mit.zoom.us/j/96799873963?pwd=P4SQakA7g3ct03eYlt88bcmkVofc7Q.1\n
 \nPassword: slice\n\n \n\nTitle: Spontaneous activity in the mouse visual 
 cortical slice: biophysical characterization and pathophysiology\n\n \n\nA
 bstract: As we continue to await the first disease-modifying treatment for
  Fragile X Syndrome (FXS)\, the leading inherited cause of intellectual di
 sability\, the search continues for novel ways to address the core pathoph
 ysiology of this neurodevelopmental disorder. In this thesis\, I present m
 y investigation of a relatively understudied form of pathophysiology that 
 arises in brain slices prepared from a mouse model of FXS\, the Fmr1-knock
 out (KO) mouse. Relative to wild-type slices\, Fmr1-KO visual cortical sli
 ces exhibit increased spontaneous activity in layer 5. Because this hypera
 ctivity phenotype is rapidly reversed by acute application of treatments k
 nown to restore a core class of Fmr1-KO pathophysiology\, elucidating its 
 cellular mechanisms could enrich our understanding of neocortical pathophy
 siology in FXS and set the stage for novel treatment strategies. Progress 
 in understanding this cellular pathophysiology requires closer examination
  of the biophysical basis of the spontaneous activity itself\, as the mech
 anisms driving this sparse form of activity in layer 5 remain relatively u
 nexplored. Here\, I find extreme sensitivity to the ionic composition of t
 he artificial cerebral spinal fluid (aCSF) bathing the slices. Lower\, mor
 e physiologic concentrations of extracellular divalent cations render extr
 atelencephalic (ET)\, not intratelencephalic (IT)\, layer 5 pyramidal neur
 ons intrinsically active by altering the activity of the persistent sodium
  current. As revealed by current-voltage (IV) curves\, ET neurons under ph
 ysiologic ionic conditions rest near a newly characterized threshold gover
 ning their steady activation. This steady activation threshold is unchange
 d in both Fmr1-KO ET and IT layer 5 neurons\, indicating that cell-intrins
 ic mechanisms do not drive hyperactivity of the Fmr1-KO layer 5 circuit an
 d prompting future exploration of synaptic pathophysiology that could unde
 rly this hyperactivity.
GEO:42.362302;-71.091766
LOCATION:Building 46\, Singleton Auditorium 46-3002
SUMMARY:Max Heinrich Thesis Defense: Spontaneous activity in the mouse visu
 al cortical slice: biophysical characterization and pathophysiology
URL;VALUE=URI:https://calendar.mit.edu/event/max-heinrich-thesis-defense-sp
 ontaneous-activity-in-the-mouse-visual-cortical-slice-biophysical-characte
 rization-and-pathophysiology
CATEGORIES:Thesis defense
END:VEVENT
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