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.
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