PMID- 16148225
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 25
IP  - 36
DP  - 2005 Sep 7
TI  - Rapid vesicular release, quantal variability, and spillover contribute to the 
      precision and reliability of transmission at a glomerular synapse.
PG  - 8173-87
AB  - The amplitude and shape of EPSC waveforms are thought to be important 
      determinants of information processing and storage in the brain, yet relatively 
      little is known about the origins of EPSC variability or how it affects synaptic 
      signaling. We investigated the stochastic determinants of AMPA receptor-mediated 
      EPSC variability at cerebellar mossy fiber-granule cell (MF-GC) connections by 
      combining multiple-probability fluctuation analysis (MPFA) and deconvolution 
      methods. The properties of MF connections with a single release site and the 
      effects of the rapidly equilibrating competitive antagonist kynurenic acid on 
      EPSCs suggest that receptors are not saturated by glutamate during a quantal 
      event and that quanta sum linearly over a wide range of release probabilities. 
      MPFA revealed an average of five vesicular release sites per MF-GC connection. 
      Our results show that the time course of vesicular release is rapid (decay, tau = 
      75 micros) and independent of release probability, introducing little jitter in 
      the shape or timing of the quantal component of the EPSC at physiological 
      temperature. Moreover, the peak vesicular release rate per release site after an 
      action potential (AP) (approximately 3 ms(-1)) is substantially higher than 
      previously reported for central synapses. Interaction of amplitude fluctuations 
      arising from quantal release and quantal size with the slower, low variability 
      spillover-mediated current produce substantial variability in EPSC shape. Our 
      simulations of MF-GC transmission suggest that quantal variability and 
      transmitter spillover extend the voltage from which AP threshold can be crossed, 
      improving reliability, and that fast vesicular release allows precise signaling 
      across MF connections with heterogeneous weights.
FAU - Sargent, Peter B
AU  - Sargent PB
AD  - Department of Physiology, University College London, London WC1E 6BT, United 
      Kingdom.
FAU - Saviane, Chiara
AU  - Saviane C
FAU - Nielsen, Thomas A
AU  - Nielsen TA
FAU - DiGregorio, David A
AU  - DiGregorio DA
FAU - Silver, R Angus
AU  - Silver RA
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (GABA Antagonists)
RN  - 0 (Pyridazines)
RN  - 99460MG420 (gabazine)
RN  - H030S2S85J (Kynurenic Acid)
RN  - H9Y79VD43J (Strychnine)
RN  - S7936QON2K (7-chlorokynurenic acid)
SB  - IM
MH  - Animals
MH  - Cerebellum/*physiology
MH  - Evoked Potentials/drug effects/physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - GABA Antagonists/pharmacology
MH  - In Vitro Techniques
MH  - Kynurenic Acid/analogs & derivatives/pharmacology
MH  - Models, Neurological
MH  - Pyridazines/pharmacology
MH  - Quantum Theory
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Strychnine/pharmacology
MH  - Synapses/*physiology
MH  - Synaptic Transmission/drug effects/*physiology
PMC - PMC6725539
EDAT- 2005/09/09 09:00
MHDA- 2006/03/03 09:00
PMCR- 2006/03/07
CRDT- 2005/09/09 09:00
PHST- 2005/09/09 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2005/09/09 09:00 [entrez]
PHST- 2006/03/07 00:00 [pmc-release]
AID - 25/36/8173 [pii]
AID - 10.1523/JNEUROSCI.2051-05.2005 [doi]
PST - ppublish
SO  - J Neurosci. 2005 Sep 7;25(36):8173-87. doi: 10.1523/JNEUROSCI.2051-05.2005.