JN Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Neurophysiol 82: 1577-1589, 1999;
0022-3077/99 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Santschi, L.
Right arrow Articles by Stanton, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santschi, L.
Right arrow Articles by Stanton, P. K.

The Journal of Neurophysiology Vol. 82 No. 3 September 1999, pp. 1577-1589
Copyright ©1999 by the American Physiological Society

Chemically Induced, Activity-Independent LTD Elicited by Simultaneous Activation of PKG and Inhibition of PKA

Linda Santschi,1 Magali Reyes-Harde,1 and Patric K. Stanton1,2

Departments of  1Neuroscience and  2Neurology, Albert Einstein College of Medicine, Bronx, New York 10461

Santschi, Linda, Magali Reyes-Harde, and Patric K. Stanton. Chemically Induced, Activity-Independent LTD Elicited by Simultaneous Activation of PKG and Inhibition of PKA. J. Neurophysiol. 82: 1577-1589, 1999. Although it is widely agreed that cyclic AMP is necessary for the full expression of long-term potentiation of synaptic strength, it is unclear whether cyclic AMP or cyclic AMP-dependent protein kinase (PKA) play roles in the induction of long-term depression (LTD). We show here that two PKA inhibitors, H-89 (10 µM) and KT5720 (1 µM), are unable to block induction of LTD at Schaffer collateral-CA1 synapses in hippocampal slices in vitro. Rather, H-89 enhanced the magnitude of LTD induced by submaximal low-frequency stimulation. Raising [cGMP] with zaprinast (20 µM), a selective type V phosphodiesterase inhibitor, reversibly depressed synaptic potentials. However, coapplication of H-89 plus zaprinast converted this to a robust LTD that depended critically on activation of cyclic GMP-dependent protein kinase (PKG). Chemically induced LTD is activity-independent because it could be induced without stimulation and in tetrodotoxin (0.5 µM). Additionally, chemical LTD did not require activation of N-methyl-D-aspartate or GABA receptors and could be reversed by LTP. Stimulus-induced LTD occluded chemical LTD, suggesting a common expression mechanism. In contrast to bath application, postsynaptic infusion of H-89 into CA1 pyramidal neurons did not enhance LTD, suggesting a presynaptic site of action. Further evidence for a presynaptic locus was supplied by experiments where H-89 applied postsynaptically along with bath application of zaprinast was unable to produce chemical LTD. Thus simultaneous presynaptic generation of cyclic GMP and inhibition of PKA is sufficient to induce LTD of synaptic transmission at Schaffer collateral-CA1 synapses.




This article has been cited by other articles:


Home page
 Learn. Mem.Home page
C. P. Bailey, R. E. Nicholls, X.-l. Zhang, Z.-y. Zhou, W. Muller, E. R. Kandel, and P. K. Stanton
G{alpha}i2 inhibition of adenylate cyclase regulates presynaptic activity and unmasks cGMP-dependent long-term depression at Schaffer collateral-CA1 hippocampal synapses
Learn. Mem., April 7, 2008; 15(4): 261 - 270.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. C. Brailoiu, S. L. Dun, E. Brailoiu, S. Inan, J. Yang, J. K. Chang, and N. J. Dun
Nesfatin-1: Distribution and Interaction with a G Protein-Coupled Receptor in the Rat Brain
Endocrinology, October 1, 2007; 148(10): 5088 - 5094.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
X.-l. Zhang, Z.-y. Zhou, J. Winterer, W. Muller, and P. K. Stanton
NMDA-Dependent, But Not Group I Metabotropic Glutamate Receptor-Dependent, Long-Term Depression at Schaffer Collateral-CA1 Synapses Is Associated with Long-Term Reduction of Release from the Rapidly Recycling Presynaptic Vesicle Pool
J. Neurosci., October 4, 2006; 26(40): 10270 - 10280.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. E. Nicholls, X.-l. Zhang, C. P. Bailey, B. R. Conklin, E. R. Kandel, and P. K. Stanton
mGluR2 acts through inhibitory G{alpha} subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses
PNAS, April 18, 2006; 103(16): 6380 - 6385.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Kiryushko, T. Kofoed, G. Skladchikova, A. Holm, V. Berezin, and E. Bock
A Synthetic Peptide Ligand of Neural Cell Adhesion Molecule (NCAM), C3d, Promotes Neuritogenesis and Synaptogenesis and Modulates Presynaptic Function in Primary Cultures of Rat Hippocampal Neurons
J. Biol. Chem., March 28, 2003; 278(14): 12325 - 12334.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Monfort, M.-D. Munoz, E. Kosenko, and V. Felipo
Long-Term Potentiation in Hippocampus Involves Sequential Activation of Soluble Guanylate Cyclase, cGMP-Dependent Protein Kinase, and cGMP-Degrading Phosphodiesterase
J. Neurosci., December 1, 2002; 22(23): 10116 - 10122.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
Y.-F. Lu and R. D. Hawkins
Ryanodine Receptors Contribute to cGMP-Induced Late-Phase LTP and CREB Phosphorylation in the Hippocampus
J Neurophysiol, September 1, 2002; 88(3): 1270 - 1278.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. K. Stanton, U. Heinemann, and W. Muller
FM1-43 Imaging Reveals cGMP-Dependent Long-Term Depression of Presynaptic Transmitter Release
J. Neurosci., October 1, 2001; 21(19): RC167 - RC167.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online