Regulation of Synaptic Facilitation by Postsynaptic Ca2+/CaM Pathways in
Hippocampal CA1 Neurons.
Wang, Jin-Hui and Paul T. Kelly.
Department of Neurobiology and Anatomy, University of Texas Medical School
Houston, Houston,Texas 77030.
APStracts 3:0027N, 1996.
SUMMARY AND CONCLUSIONS
1). Current- and voltage-clamp recordings with simultaneous field potential
recordings were used to study the cellular and molecular mechanisms that
contribute to synaptic facilitation at CA1 synapses in rat hippocampal slices.
Microelectrodes used for intracellular recordings were also used to inject
modulators of intracellular signal pathways into postsynaptic CA1 neurons. 2).
Paired-pulse stimulation at constant stimulus intensity was used to analyze
the relationship between the first evoked response (R1) and the absolute value
of paired-pulse synaptic facilitation (R2-R1). The magnitudes of these two
measures were inversely correlated. Compared to synapses that control motor
functions, the synapses of CA1 pyramidal neurons did not exhibit accumulative
synaptic facilitation during repetitive stimulation, which is often believed
to be mediated by presynaptic residual Ca2+. 3). During studies on the
cellular location of mechanisms contributing to synaptic facilitation, we
observed that postsynaptic injections of 1,2-bis(2-aminophenoxy)-ethane-
N,N,Ní,Ní-tetraacetic acid (BAPTA), or [Ala286]CaMKII281-302 (a CaM-KII
inhibitor peptide) prevented the decreases in paired-pulse facilitation (PPF)
and synaptic potentiation induced by elevating extracellular Ca2+. These
results show that raising extracellular Ca2+ enhances synaptic transmission in
part by activating postsynaptic Ca2+ signal pathways. 4). The injection of
Ca2+/CaM into postsynaptic neurons significantly decreased PPF in 50 out of 57
experiments while inducing synaptic potentiation; the Ca2+/CaM-induced
synaptic potentiation and PPF attenuation occluded subsequent high Ca2+-
induced enhancements of synaptic transmission. The changes in PPF induced by
postsynaptic injections of Ca2+/CaM were inversely correlated with R1
potentiation. 5). The decreases in PPF induced by postsynaptic Ca2+/CaM
injections were prevented by co-injecting pseudosubstrate inhibitors or
substrate peptides of Ca2+/CaM-dependent protein kinase II (CaM-KII) and
protein kinase C (PKC), and were reversed by subsequent application of
cyclothiazide (a blocker of AMPA receptor desensitization). 6). Our results
reveal that postsynaptic Ca2+/CaM signal pathways can modulate synaptic
facilitation in the central nervous system (CNS), and the activities of CaM-
KII and PKC are involved in this modulation. The physiological significance of
such modulation is that synaptic strength could be potentiated by activation
of Ca2+/CaM pathways during integration of important sensory input (e.g.,
learning and memory), whereas decreases in synaptic facilitation may protect
synaptic transmission during extreme stimulation so that neuronal signal
mechanisms can more accurately code neural information.
Received 11 October 1995; accepted in final form 8 January 1995.
APS Manuscript Number J676-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96