Attenuation of Paired-Pulse Facilitation Associated with Synaptic
Potentiation Mediated by Postsynaptic Mechanisms.
Jin-Hui Wang and Paul T. Kelly.
Department of Neurobiology and Anatomy, University of Texas Medical School
at Houston, Houston, Texas 77030.
APStracts 4:145N, 1997.
ABSTRACT
The relationship between paired-pulse facilitation (PPF) and synaptic
potentiation induced by various protocols, and their cellular and molecular
mechanisms were examined by extracellular field potential and current- or
voltage-clamp recordings at CA1 synapses in rat hippocampal slices.
Microelectrodes were used for both intracellular recordings and injections of
modulators of calcium (Ca2+) and Ca2+/calmodulin (CaM) signaling pathways into
postsynaptic neurons.
Basal synaptic transmission was not accompanied by changes in PPF. Tetanic
stimulation induced long-term potentiation (LTP) of synaptic transmission and
attenuated PPF. Experiments stimulating two independent Schaffer
collateral/commisural (S/C) pathways showed that PPF attenuation and tetanus-
LTP were pathway specific. Postsynaptic injections of pseudosubstrate
inhibitors of CaM-KII/PKC, [Ala286]CaMKII286-302 plus PKC19-31, almost
completely attenuated tetanus-LTP and reversed PPF attenuation, but did not
affect synaptic transmission and PPF under basal conditions. Postsynaptic
injections of heparin and dantrolene (inhibitors of IP3 and ryanodine
receptors at intracellular Ca2+ stores) prevented tetanus-LTP induction and
PPF attenuation.
Postsynaptic injections of calcineurin (CaN) inhibitors, CaN autoinhibitory
peptide (CaN-AIP) or FK-506, enhanced synaptic transmission and decreased PPF.
CaN-inhibited synaptic potentiation and PPF attenuation were unaffected by D(-
)-2-Amino-5-phosphonopentanoic (D-AP5), but blocked by co-injecting 1,2-bis(2-
aminophenoxy)-ethane-N,N,N’,N’-tetraacetic acid (BAPTA), heparin plus
dantrolene, calmodulin-binding peptide (CBP), or [Ala286]CaMKII281-302 plus
PKC19-31. PPF attenuation associated with tetanus-LTP or CaN-inhibited
synaptic potentiation resulted from smaller increases in the potentiation of
the second synaptic responses (R2) compared to the potentiation of the first
responses (R1).
Our results indicate that PPF attenuation is associated with synaptic
potentiation mediated by postsynaptic mechanisms, and postsynaptic Ca2+/CaM
signaling pathways play a dual role in synaptic plasticity. CaN activity
limits synaptic transmission under basal conditions, whereas the activation of
Ca2+-dependent protein kinases enhances synaptic transmission and attenuates
PPF at central synapses.
Received 2 April 1997; accepted in final form 1 July 1997.
APS Manuscript Number J270-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997