PMID- 11906520
OWN - NLM
STAT- MEDLINE
DCOM- 20020523
LR  - 20220317
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 15
IP  - 5
DP  - 2002 Mar
TI  - The speeding of EPSC kinetics during maturation of a central synapse.
PG  - 785-97
AB  - Several factors contribute to the shape of excitatory postsynaptic currents 
      (EPSCs) in CNS neurons, among them the kinetics of presynaptic release, 
      transmitter clearance, and the properties and distribution of postsynaptic 
      receptors. The decays of AMPA receptor-mediated EPSCs at rat cerebellar mossy 
      fibre-granule cell (MF-gc) synapses follow a bi-exponential time-course. The fast 
      component dominates the decay, accounting for 84-94% of the peak amplitude. Here 
      we show that both components of decay, and also the risetimes, became faster 
      during postnatal maturation. At adult, but not immature, synapses, the risetimes 
      and decays of evoked multiquantal EPSCs were similar to those of monoquantal 
      miniature (m)EPSCs. The faster risetimes at mature synapses reflected increased 
      synchrony of multivesicular release, whereas the faster decays appeared to 
      reflect changes in the properties of postsynaptic receptors. Inhibition of 
      glutamate uptake was without effect on evoked EPSCs at both ages. Furthermore, 
      after slowing receptor desensitization with cyclothiazide, the EPSCs at mature 
      synapses decayed as slowly as EPSCs at immature synapses, suggesting that faster 
      glutamate clearance does not account for the developmental speeding of EPSC 
      decay. Our results support previous conclusions that glutamate clearance and 
      receptor deactivation are important determinants of the fast decay component at 
      immature synapses. Desensitization becomes increasingly important during 
      development and plays a major role in shaping EPSC decay at mature synapses.
FAU - Wall, Mark J
AU  - Wall MJ
AD  - Department of Pharmacology, University of Bristol, University Walk, Bristol, BS8 
      1TD, UK.
FAU - Robert, Antoine
AU  - Robert A
FAU - Howe, James R
AU  - Howe JR
FAU - Usowicz, Maria M
AU  - Usowicz MM
LA  - eng
GR  - NS37904/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Benzothiadiazines)
RN  - 0 (Dicarboxylic Acids)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptors, AMPA)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 99319-03-6 (pyrrolidine-2,4-dicarboxylic acid)
RN  - P71U09G5BW (cyclothiazide)
SB  - IM
MH  - Aging/metabolism
MH  - Amino Acid Transport System X-AG/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Antihypertensive Agents/pharmacology
MH  - Benzothiadiazines/pharmacology
MH  - Cell Differentiation/*physiology
MH  - Cells, Cultured
MH  - Cerebellum/drug effects/*growth & development/*metabolism
MH  - Dicarboxylic Acids/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/*physiology
MH  - Glutamic Acid/metabolism/pharmacology
MH  - Kinetics
MH  - Male
MH  - Nerve Fibers/drug effects/metabolism
MH  - Neurons/drug effects/*metabolism
MH  - Neurotransmitter Uptake Inhibitors/pharmacology
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, AMPA/drug effects/*metabolism
MH  - Synapses/drug effects/*metabolism
MH  - Synaptic Transmission/physiology
MH  - Synaptic Vesicles/drug effects/metabolism
EDAT- 2002/03/22 10:00
MHDA- 2002/05/25 10:01
CRDT- 2002/03/22 10:00
PHST- 2002/03/22 10:00 [pubmed]
PHST- 2002/05/25 10:01 [medline]
PHST- 2002/03/22 10:00 [entrez]
AID - 1910 [pii]
AID - 10.1046/j.1460-9568.2002.01910.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2002 Mar;15(5):785-97. doi: 10.1046/j.1460-9568.2002.01910.x.