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X-WR-CALNAME:Dimitra Vardalaki Thesis Defense: Functional and ultrastructur
 al investigation of mouse and human dendritic spines
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20260514T192127Z
UID:tag:localist.com\,2008:EventInstance_42853722322128
DTSTART:20230413T150000Z
DTEND:20230413T160000Z
DESCRIPTION:Date:Time: Thursday\, April 13th at 11:00AM ET\n\nLocation: MIT
 \, Picower Seminar Room 46-3310\n\nThesis Title: Functional and ultrastruc
 tural investigation of mouse and human dendritic spines\n\nAbstract: Dendr
 itic spines are the physical site of the majority of excitatory synaptic c
 onnections in the mammalian brain. Their complex morphological attributes 
 and protein composition have inspired decades of theoretical and experimen
 tal work on how classes of dendritic spines differentially sculpt input pr
 ocessing and plasticity. The technical challenge of tethering physiologica
 l measurements of synaptic strength to spine morphology and protein expres
 sion in specific cell types leaves many open questions for the field. Here
 \, we combine super-resolution protein imaging and patch-clamp electrophys
 iology to investigate the formation of nascent connections in the adult mo
 use cortex\, and we develop a new method to apply these techniques to huma
 n neurons. In the first project presented\, we used super-resolution prote
 in imaging and patch-clamp electrophysiology to identify filopodia as the 
 structural substrate for silent synapses in adult neocortex. Of 2\,234 spi
 ny synapses from adult mouse layer 5 pyramidal neurons\, a surprisingly la
 rge fraction (~25%) lacked AMPA receptors. These putative silent synapses 
 were located at the tips of thin dendritic protrusions that lack the disti
 nct head of conventional spines\, known as filopodia\, which were more abu
 ndant in adult cortex by an order of magnitude than previously believed (c
 ompromising ~30% of all dendritic protrusions). Physiological experiments 
 revealed that filopodia do indeed lack AMPAR-mediated transmission\, but t
 hey exhibit NMDAR-mediated synaptic transmission. We further showed that f
 unctionally silent synapses on filopodia can be unsilenced via Hebbian pla
 sticity\, recruiting new active connections into a neuron’s input matrix
 . In the second project\, we developed Patch2MAP to perform super-resoluti
 on imaging of proteins localized in the 3D morphology of any cell type in 
 human tissue (or in any other species) without the need for exogenous prot
 ein expression. Our method\, which combines patch-clamp electrophysiology 
 with epitope-preserving magnified analysis of proteome (eMAP)\, further al
 lows for correlation of physiological properties with subcellular protein 
 expression. We applied Patch2MAP to individual spiny synapses in human cor
 tical pyramidal neurons and demonstrated that electrophysiological AMPA-to
 -NMDA receptor ratios correspond tightly to respective protein expression 
 levels. Taken together\, the combination of protein imaging and physiologi
 cal measurements expand our understanding on how the interplay of structur
 e and protein content of spiny synapses shape synaptic input and open new 
 avenues for a comprehensive investigation of synaptic function in humans.\
 n\nThesis Supervisor: Mark T. Harnett\n\nThesis Committee: Mark Bear\, Mor
 gan Sheng\, Bernardo Sabatini
LOCATION:MIT\, Picower Seminar Room\, 46-3310
SUMMARY:Dimitra Vardalaki Thesis Defense: Functional and ultrastructural in
 vestigation of mouse and human dendritic spines
URL;VALUE=URI:https://calendar.mit.edu/event/dimitra_vardalaki_thesis_defen
 se_functional_and_ultrastructural_investigation_of_mouse_and_human_dendrit
 ic_spines
CATEGORIES:Thesis defense
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