Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein

AUTOR(ES)

Murphy, Diane D.

FONTE

The National Academy of Sciences of the USA

RESUMO

While evidence has accumulated in favor of cAMP-associated genomic involvement in long-term synaptic plasticity, the mechanisms downstream of the activated nucleus that underlie these changes in neuronal function remain mostly unknown. Dendritic spines, the locus of excitatory interaction among central neurons, are prime candidates for long-term synaptic modifications. We now present evidence that links phosphorylation of the cAMP response element binding protein (CREB) to formation of new spines; exposure to estradiol doubles the density of dendritic spines in cultured hippocampal neurons, and concomitantly causes a large increase in phosphorylated CREB and in CREB binding protein. Blockade of cAMP-regulated protein kinase A eliminates estradiol-evoked spine formation, as well as the CREB and CREB binding protein responses. A specific antisense oligonucleotide eliminates the phosphorylated CREB response to estradiol as well as the formation of new dendritic spines. These results indicate that CREB phosphorylation is a necessary step in the process leading to generation of new dendritic spines.

Documentos Relacionados

• Odorants induce the phosphorylation of the cAMP response element binding protein in olfactory receptor neurons
• cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase.
• Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation.
• Activated cAMP Response Element Binding Protein Is Overexpressed in Human Mesotheliomas and Inhibits Apoptosis
• D2 dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons