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Single cell analysis of activity-dependent cyclic AMP-responsive element-binding protein phosphorylation during long-lasting long-term potentiation in area CA1 of mature rat hippocampal-organotypic cultures.
- Source :
-
Neuroscience [Neuroscience] 2005; Vol. 131 (3), pp. 601-10. - Publication Year :
- 2005
-
Abstract
- Phosphorylation of the transcription factor cyclic AMP (cAMP)-response element-binding protein (CREB) has been implicated in long-term synaptic plasticity and memory, and its activation has been proposed to be required for the maintenance of long-term potentiation (LTP). The previously described temporal dynamics of CREB phosphorylation during the maintenance of LTP showed differences between experimental models. In the present study the level of CREB phosphorylation was evaluated in organotypic hippocampal slices from young adult rats (P25-30) after long-lasting LTP was induced. Immunohistochemistry and confocal imaging were used to determine the ratio between non-phosphorylated and phosphorylated CREB at a single cell resolution, revealing not only the temporal dynamics but also the extent of CREB phosphorylation. The activation of CREB after LTP-induction was compared with cAMP-activation after bath application of forskolin. An increase in cAMP by forskolin resulted in a persistent, uniform increase of the phosphorylated CREB (pCREB/CREB immunofluorescence ratio) in all hippocampal principal neurons. In contrast, the induction of long-lasting LTP in CA1 was accompanied by a local increase in the pCREB/CREB ratio. Both CREB activation and LTP induction in mature cultured slices required N-methyl-D-aspartate (NMDA) receptor activation. CREB phosphorylation continued to increase for 4 h during LTP maintenance. This sustained activation is in contrast to previous observations in acutely prepared slices and supports the hypothesis that CREB plays an important role during the late phases of LTP.
- Subjects :
- Animals
Animals, Newborn
Colforsin pharmacology
Electric Stimulation methods
Excitatory Amino Acid Agonists pharmacology
Excitatory Postsynaptic Potentials drug effects
Excitatory Postsynaptic Potentials radiation effects
Immunohistochemistry methods
In Vitro Techniques
Long-Term Potentiation drug effects
Long-Term Potentiation radiation effects
Male
Microscopy, Confocal methods
Neurons physiology
Neurons radiation effects
Phosphorylation drug effects
Phosphorylation radiation effects
Rats
Serine metabolism
Time Factors
Valine pharmacology
Cerebral Cortex cytology
Cyclic AMP Response Element-Binding Protein physiology
Hippocampus cytology
Long-Term Potentiation physiology
Neurons drug effects
Valine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 131
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 15730866
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2004.12.002