TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity

doi:10.1073/pnas.0607524104

TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity

*Center for Psychiatric Neuroscience and
^† Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, CH-1008 Prilly–Lausanne, Switzerland; and
^‡Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

Edited by Floyd E. Bloom, The Scripps Research Institute, La Jolla, CA, and approved January 19, 2007 (received for review August 30, 2006)

Abstract

A key feature of memory processes is to link different input signals by association and to preserve this coupling at the level of synaptic connections. Late-phase long-term potentiation (L-LTP), a form of synaptic plasticity thought to encode long-term memory, requires gene transcription and protein synthesis. In this study, we report that a recently cloned coactivator of cAMP-response element-binding protein (CREB), called transducer of regulated CREB activity 1 (TORC1), contributes to this process by sensing the coincidence of calcium and cAMP signals in neurons and by converting it into a transcriptional response that leads to the synthesis of factors required for enhanced synaptic transmission. We provide evidence that TORC1 is involved in L-LTP maintenance at the Schaffer collateral–CA1 synapses in the hippocampus.

Footnotes

^§To whom correspondence should be addressed at:
Centre de Neurosciences Psychiatriques, Site de Cery, CH-1008 Prilly-Lausanne, Switzerland.
E-mail: Jean-Rene.Cardinaux{at}chuv.ch
Author contributions: K.A.K. and P.S. contributed equally to this work; K.A.K., P.S., K.Q.D., P.J.M., O.H., and J.-R.C. designed research; K.A.K., P.S., M.S., and J.-R.C. performed research; K.A.K., P.S., and J.-R.C. analyzed data; and K.A.K., P.J.M., and J.-R.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0607524104/DC1.
Abbreviations:

ACF,

artificial cerebrospinal fluid;

BDNF,

brain-derived neurotrophic factor;

CBP,

CREB-binding protein;

CRE,

cAMP-response element;

CREB,

CRE-binding protein;

CsA,

cyclosporine A;

FSK,

forskolin;

HFS,

high-frequency stimulation;

L-LTP,

late-phase long-term potentiation;

LMB,

leptomycin B;

shRNA,

short hairpin RNA;

TORC,

transducer of regulated CREB activity.