Shared calcium signalling pathways in the induction of long-term
potentiation and synaptic disinhibition in CA1 pyramidal cell dendrites.
Wang, Jin-Hui & Armin Stelzer.
From.
APStracts 2:0322N, 1995.
SUMMARY AND CONCLUSIONS
1) Calcium signalling pathways were examined in the induction of long-term
synaptic disinhibition following tetanization. Effects of tetanization on GABA
A receptor-mediated inhibitory responses were measured and compared with
excitatory responses under experimental conditions previously used for
examining induction mechanisms of NMDA-dependent LTP. Intracellular recordings
were performed in current- and discontinuous single-electrode voltage-clamp
(dSEVC) modes in CA1 pyramidal cell apical dendrites in hippocampal slices of
adult guinea-pigs using sharp electrodes. Test pulses and tetanic stimuli were
applied to the Schaffer collateral fibers in stratum radiatum. 2) Under
standard control conditions (3 M KAc in the recording pipette and ACSF as
extracellular solution), tetanization-induced sustained increases of
excitatory responses were accompanied by marked decreases of parameters of
GABA A -mediated synaptic inhibition: at 40 minutes following tetanization
(post-tetanus 40, PT 40), orthodromically evoked EPSP peak amplitudes were on
average 195 + 15% and EPSCs 166 + 10% of pretetanus controls. Peak amplitudes
of orthodromically evoked IPSPs were 30 + 5% and IPSCs 21 + 4% at PT 40.
Synaptic GABA A conductances (measured as chord conductances) were reduced to
22 + 4% at PT 40. Iontophoretic GABA A responses measured as conductance
changes were 28 + 4% of pretetanus controls at PT 40. 3) A role of NMDA
receptors in induction of long-term synaptic disinhibition was tested by
preventing NMDA receptor activation a) by pharmacological means and b) by
holding the membrane clamped at -80 mV (in dSEVC) during tetanization. In the
presence of the NMDA-receptor antagonist D-AP5 (10-40 [mu]M), orthodromically
evoked EPSP amplitudes were 107 + 9%, EPSCs 104 + 6%, GABA A -mediated IPSPs
88 + 8%, IPSCs 97 + 8%, synaptic GABA A conductances 84 + 9% and iontophoretic
GABA A conductances 102 + 13% at PT 40. In recordings in which the dendritic
membrane potential was clamped at -80 mV during tetanization, orthodromically
evoked peak amplitudes of EPSPs were 105 + 11%, EPSCs 102 + 8, IPSPs 103 + 4%,
IPSCs 102 + 5%, GABA A chord conductances 101 + 9% and iontophoretically
evoked GABA A conductances 105 + 5% at PT 40. 4) In recordings in which the
intracellular pipette was preloaded with the Ca 2+ chelator BAPTA (5 mM),
long-term changes of synaptic transmission (increases of excitation, decreases
of synaptic inhibition) were prevented. At PT 40, EPSP peak amplitudes were 93
+ 7%, EPSCs 115 + 6%, IPSPs 115 + 9%, IPSCs 117 + 8% and synaptic GABA A
conductances were 108 + 17%. Iontophoretic conductances at PT 40 were 109 + 9%
over pretetanus controls when recorded with BAPTA containing electrodes. 5) In
recordings in which the intracellular pipette was preloaded with cypermethrin,
a potent and selective inhibitor of phosphatase 2B (PP-2B), respective long-
term changes of synaptic transmission (increases of excitation, decreases of
synaptic inhibition) were prevented. At PT 40, EPSP peak amplitudes were 98 +
6, EPSCs 105 + 10%, IPSPs 99 + 5%, IPSCs 104 + 7% and GABA conductances were
97 + 6% over pretetanus controls in cypermethrin containing recordings. 6) In
conclusion, the data presented demonstrate shared cellular pathways in the
induction of both, LTP and long-term synaptic disinhibition in apical
dendrites of CA1 pyramidal cells following tetanization of the Schaffer
collaterals. The close temporal long-term correlation between potentiation of
excitatory and decreases of inhibitory synaptic responses under various
experimental conditions provide evidence for the notion of synaptic
disinhibtion contributing to NMDA-dependent pyramidal cell LTP in CA1.
Received 9 August 1995; accepted in final form 26 October 1995.
APS Manuscript Number J523-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95