Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity

K Deisseroth; H Bito; R W Tsien

doi:10.1016/s0896-6273(00)80026-4

Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity

Neuron. 1996 Jan;16(1):89-101. doi: 10.1016/s0896-6273(00)80026-4.

Authors

K Deisseroth¹, H Bito, R W Tsien

Affiliation

¹ Department of Molecular and Cellular Physiology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, California 94305, USA.

PMID: 8562094
DOI: 10.1016/s0896-6273(00)80026-4

Abstract

Phosphorylation of the transcription factor CREB is thought to be important in processes underlying long-term memory. It is unclear whether CREB phosphorylation can carry information about the sign of changes in synaptic strength, whether CREB pathways are equally activated in neurons receiving or providing synaptic input, or how synapse-to-nucleus communication is mediated. We found that Ca(2+)-dependent nuclear CREB phosphorylation was rapidly evoked by synaptic stimuli including, but not limited to, those that induced potentiation and depression of synaptic strength. In striking contrast, high frequency action potential firing alone failed to trigger CREB phosphorylation. Activation of a submembranous Ca2+ sensor, just beneath sites of Ca2+ entry, appears critical for triggering nuclear CREB phosphorylation via calmodulin and a Ca2+/calmodulin-dependent protein kinase.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Action Potentials
Animals
Calcium / physiology
Calcium-Calmodulin-Dependent Protein Kinases / physiology
Calmodulin / physiology
Cell Compartmentation
Cell Nucleus / physiology
Cells, Cultured
Chelating Agents / pharmacology
Cyclic AMP Response Element-Binding Protein / metabolism*
Egtazic Acid / analogs & derivatives
Egtazic Acid / pharmacology
Hippocampus / physiology*
Long-Term Potentiation / physiology*
Nerve Tissue Proteins / metabolism*
Nerve Tissue Proteins / physiology
Phosphorylation
Protein Processing, Post-Translational*
Rats
Rats, Sprague-Dawley
Recombinant Proteins / metabolism
Signal Transduction / drug effects
Signal Transduction / physiology*
Synapses / physiology
Synaptic Transmission / drug effects
Synaptic Transmission / physiology*

Substances

Calmodulin
Chelating Agents
Cyclic AMP Response Element-Binding Protein
Nerve Tissue Proteins
Recombinant Proteins
Egtazic Acid
Calcium-Calmodulin-Dependent Protein Kinases
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Calcium