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

• Published in: Proceedings of the National Academy of Sciences
• Main Authors: Yu, Tzu-ping, McKinney, Sheri, Lester, Henry A., Davidson, Norman
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: National Academy of Sciences 2001
• Subjects: SYNAPTIC ACTIVATION CAUSES; DEPENDENT PROTEIN-KINASE; HIPPOCAMPAL CA1 NEURONS; CYCLIC-AMP; LATE-PHASE; LTP; ADENOSINE; TRANSMISSION; STIMULATION; CULTURES; Davidson; sami
• Online Access: https://doi.org/10.1073/pnas.091093998; https://www.ncbi.nlm.nih.gov/pmc/PMC33198

cAMP induces a protein-synthesis-dependent late phase of longterm potentiation (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 cell pairs in organotypic hippocampal slice cultures. After bath application of the membrane-permeable cAMP analog adenosine 3 ' ,5 ' -cyclic monophosphorothioate, Sp isomer (Sp-cAMPS), synaptic transmission was enhanced for at least 2 h. Consistent with previous findings, the late phase of LTP requires activation of cAMP-dependent protein kinase A and protein synthesis. There 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 protein synthesis, in addition, the cAMP-induced LTP is associated with a reduction of paired-pulse facilitation, suggesting that presynaptic modification may be involved. Furthermore, we found that Sp-cAMPS induced LTD in slices pretreated with picrotoxin, a gamma -aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends on protein synthesis and protein phosphatase(s) and is accompanied by an increased ratio of failed synaptic transmission. These results suggest that GABA(A) receptors can modulate the effect of cAMP on synaptic transmission and thus determine the direction of synaptic plasticity. © 2001 by the National Academy of Sciences. Contributed by Norman Davidson, February 23, 2001. We thank Sami Barghshoon for preparing the slice cultures. This work was supported by the National Institutes of Health and the McKnight Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. Published - PUTpnas01.pdf