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Postsynaptic Mechanisms Are Essential for Forskolin-Induced Potentiation of Synaptic Transmission

Sokolova, Irina V. and Lester, Henry A. and Davidson, Norman (2006) Postsynaptic Mechanisms Are Essential for Forskolin-Induced Potentiation of Synaptic Transmission. Journal of Neurophysiology, 95 (4). pp. 2570-2579. ISSN 0022-3077. doi:10.1152/jn.00617.2005. https://resolver.caltech.edu/CaltechAUTHORS:20200427-123125281

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Abstract

It has been demonstrated that stimulation of protein kinase A (PKA) results in enhanced synaptic transmission in the hippocampus and other brain areas. To investigate mechanisms of the PKA-mediated potentiation of synaptic transmission, we used rat hippocampal embryonic cultures. In low-density cultures, paired recordings under the perforated patch demonstrated that 15-min forskolin treatment produced long-lasting potentiation of evoked excitatory postsynaptic currents (eEPSCs) mediated by the cAMP/PKA pathway. eEPSC amplitudes increased to 240 ± 10% of baseline after 15 min of forskolin treatment (early). After forskolin washout, eEPSCs declined to a potentiated level. Potentiation was sustained for ≥85 min after forskolin washout and, 60 min after forskolin washout, constituted 152 ± 7% of baseline (late potentiation). Disruption of presynaptic processes with the whole cell configuration and internal solution containing PKA inhibitor peptide did not affect forskolin-induced potentiation. Disruption of postsynaptic processes, in contrast, impaired early potentiation and abolished late potentiation. Study of mEPSCs confirmed the contribution of postsynaptic mechanisms. Forskolin-induced enhancement of mEPSC frequency observed under the perforated patch was attenuated by the whole cell configuration. Forskolin also induced an increase of mEPSC amplitudes in the perforated patch, but not in the whole cell, experiments. Potentiation of eEPSCs was not activity dependent, persisting in the absence of stimulation. NMDA receptor blockade did not abolish forskolin-induced potentiation. In summary, we demonstrate that forskolin-induced potentiation of eEPSCs was mediated by postsynaptic mechanisms, presumably by upregulation of AMPA receptors by phosphorylation.


Item Type:Article
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URLURL TypeDescription
https://doi.org/10.1152/jn.00617.2005DOIArticle
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2006 by the American Physiological Society. Received 13 June 2005; Accepted 22 December 2005; Published online 1 April 2006; Published in print 1 April 2006. We are thankful to S. McKinney for neuronal cultures, A. Kleschevnikov for discussion and valuable suggestions, and K. Diba for help in preparing the manuscript. This research was supported by National Institute of Mental Health Grant MH-49176. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHMH-49176
Issue or Number:4
DOI:10.1152/jn.00617.2005
Record Number:CaltechAUTHORS:20200427-123125281
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200427-123125281
Official Citation:Postsynaptic Mechanisms Are Essential for Forskolin-Induced Potentiation of Synaptic Transmission Irina V. Sokolova, Henry A. Lester, and Norman Davidson Journal of Neurophysiology 2006 95:4, 2570-2579; doi: 10.1152/jn.00617.2005
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102805
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:27 Apr 2020 20:01
Last Modified:16 Nov 2021 18:15

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