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DTSTART:20260329T030000
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DTSTAMP:20260724T080545Z
UID:1785934800@ist.ac.at
DTSTART:20260805T150000
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DESCRIPTION:Speaker: Silvia Jamrichova\nhosted by Maria Ibáñez\nAbstract:
  A fundamental question in neuroscience is how the biophysical properties 
 of synapses shape higher network computations. The mossy fiber synapse is 
 a key synapse of the trisynaptic circuit of the hippocampus\, a brain regi
 on central to the encoding and retrieval of declarative memory. Its unique
  size\, large vesicle pool\, wide range of plasticity\, striking "detonato
 r" properties\, and involvement in several higher-order computations\, nam
 ely pattern separation and pattern completion\, make it an ideal model for
  studying synaptic mechanisms with direct relevance to memory and its impa
 irments.Despite extensive study over the years\, however\, key questions r
 emain unresolved: the molecular identity of the Ca² sensors driving its d
 istinct modes of release and plasticity\, and whether its fundamental prop
 erties are preserved in the human brain.Thanks to newly generated transgen
 ic mice and a method of direct presynaptic patch-clamp recordings from mos
 sy fiber boutons\, we used a combination of electrophysiological\, imaging
  and behavioral methods to investigate the role of synaptotagmins in timin
 g of transmission and plasticity at this synapse.We found that Syt1 is the
  primary Ca² sensor for synchronous release\, with a major trigger and mi
 nor clamping function of neurotransmitter release. Syt1 deletion led to an
  increase in asynchronous release converting the teacher synapse from a te
 mporally precise conditional detonator to an asynchronous one. Moreover\, 
 at the behavioral level\, desynchronized release selectively impaired patt
 ern completion\, while pattern separation remained intact\, demonstrating 
 that disruption of its precise timing and strength leads to selective impa
 irments in behaviorally relevant hippocampal computations in mice. Interes
 tingly\, our data did not support a proposed role for Syt7 in either async
 hronous release\, or facilitation or pool refilling\, leaving its function
  at this synapse enigmatic.Furthermore\, utilizing non-sclerotic tissue ob
 tained from temporal lobe epilepsy patients undergoing brain surgery\, we 
 discovered several notable species differences: human mossy fiber boutons 
 display larger vesicle pools and amplitude responses\, and — strikingly 
 — exhibit full detonator properties in CA3. Furthermore\, mossy fiber sy
 napses targeting CA4 neurons lack such properties\, suggesting a distinct 
 functional role at this projection.Together\, the findings presented in th
 is thesis shed light on the molecular mechanisms underlying information pr
 ocessing at the hippocampal mossy fiber synapse\, with implications for ou
 r understanding of memory\, and reveal both conserved and distinct synapti
 c properties between mice and humans\, suggesting that human mossy fibers 
 are not a simple scaled version of their rodent counterpart.
LOCATION:Central Bldg / O1 / Lecture Hall (I02.O1.014) and Zoom\, ISTA
ORGANIZER:
SUMMARY:Silvia Jamrichova: Thesis Defense: Timing and strength of synaptic 
 transmission at hippocampal mossy fiber synapses in mice and humans
URL:https://talks-calendar.ista.ac.at/events/6570
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