gamma-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses

cAMP induces a protein-synthesis-dependent late phase of longterm potentiat ion (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 c ell pairs in organotypic hippocampal slice cultures. After bath application of the membrane-permeable cAMP analog adenosine 3 ' ,5 ' -cyclic monophosp horothioate, Sp isomer (Sp-cAMPS), synaptic transmission was enhanced for a t least 2 h, Consistent with previous findings, the late phase of LTP requi res activation of cAMP-dependent protein kinase A and protein synthesis. Th ere is also an early phase of LTP induced by cAMP; the early phase depends on protein kinase A but, in contrast to the later phase, does not require p rotein synthesis, in addition, the cAMP-induced LTP is associated with a re duction of paired-pulse facilitation, suggesting that presynaptic modificat ion may be involved. Furthermore, we found that Sp-cAMPS induced LTD in sli ces pretreated with picrotoxin. a gamma -aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends on protein synthesis and pro tein phosphatase(s) and is accompanied by an increased ratio of failed syna ptic transmission, These results suggest that GABA(A) receptors can modulat e the effect of cAMP on synaptic transmission and thus determine the direct ion of synaptic plasticity.