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DTSTART:20191027T020000
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DTSTAMP:20260404T093556Z
UID:5dc3e5a8ec0b1021368885@ist.ac.at
DTSTART:20191114T150000
DTEND:20191114T160000
DESCRIPTION:Speaker: Jason Rothman\nhosted by Peter Jonas\nAbstract: Hippoc
 ampal and cerebellar mossy fiber terminals (hMFTs and cMFTs) form some of 
 the largest synapses in the central nervous system\, having numerous varic
 osities\, active zones (AZs) and thousands of synaptic vesicles. However\,
  despite a similar morphology on a gross anatomical level\, cMFTs and hMFT
 s exhibit distinct functional properties with respect to synaptic transmis
 sion\, plasticity and their roles within their respective neural networks.
  To investigate whether vesicle mobility might play an important role in t
 he functional distinction of these two large synapses\, we performed fluor
 escence recovery after photobleaching (FRAP) experiments on hMFTs and cMFT
 s in brain slices from VGLUT1-Venus knock-in mice. Our results show a 9-fo
 ld lower vesicle mobility in hMFTs compared to cMFTs. Moreover\, the immob
 ile-vesicle fraction is at least twice as large in hMFTs compared to cMFTs
 \, which may explain in part the lower vesicle mobility in hMFTs. Bath app
 lication of roscovitine\, a CDK5 inhibitor\, produced a larger reduction o
 f the immobile-vesicle fraction in hMFTs compared to cMFTs\, suggesting sy
 napsin-based vesicle binding in hMFTs but not cMFTs. Next\, we investigate
 d whether structural properties of hMFTs and cMFTs underlay the 9-fold dif
 ference in vesicle mobility. Quantitative analysis of electron micrograph 
 (EM) data indicates the vesicle density is similar in hMFTs and cMFTs\, an
 d therefore cannot account for the difference in vesicle mobility. Monte C
 arlo FRAP simulations confirm the immobile-vesicle fraction is larger in h
 MFTs (58%) compared to cMFTs (25%). While a larger immobile-vesicle fracti
 on can account for the lower vesicle mobility in hMFTs\, due to steric and
  hydrodynamic interactions\, our analysis indicates it can only account fo
 r a 2 to 3-fold reduction in vesicle mobility. This suggests Dcyto\, the d
 iffusion constant of a single vesicle within the cytomatrix\, is lower in 
 hMFTs than in cMFTs\, by about 3-fold. Finally\, to investigate the effect
 s of a lower vesicle mobility in hMFTs on synaptic transmission\, we simul
 ated vesicle diffusion in the vicinity of AZs\, where vesicle locations an
 d AZ geometries were derived from 3D EM reconstructions. Results show an ~
 2-fold higher vesicle supply rate to AZs in hMFTs compared to cMFTs at ear
 ly times (< 2 ms)\, due to a larger AZ surface area (~4-fold larger)\, and
  comparable supply rates at intermediate (100 ms) and late times (50-100 s
 ). Hence\, the larger AZ surface area in hMFTs counteracts the lower vesic
 le mobility\, resulting in a vesicle supply rate comparable to that in cMF
 Ts.
LOCATION:Mondi Seminar Room 2\, Central Building\, ISTA
ORGANIZER:ekrallib@ist.ac.at
SUMMARY:Jason Rothman: A Comparison of vesicle mobility in hippocampal and 
 cerebellar mossy fiber synaptic terminals
URL:https://talks-calendar.ista.ac.at/events/2406
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