Article

Expression of Constitutively Active CREB Protein Facilitates the Late Phase of Long-Term Potentiation by Enhancing Synaptic Capture

Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
Cell (Impact Factor: 32.24). 04/2002; 108(5):689-703. DOI: 10.1016/S0092-8674(02)00657-8
Source: PubMed

ABSTRACT

Restricted and regulated expression in mice of VP16-CREB, a constitutively active form of CREB, in hippocampal CA1 neurons lowers the threshold for eliciting a persistent late phase of long-term potentiation (L-LTP) in the Schaffer collateral pathway. This L-LTP has unusual properties in that its induction is not dependent on transcription. Pharmacological and two-pathway experiments suggest a model in which VP16-CREB activates the transcription of CRE-driven genes and leads to a cell-wide distribution of proteins that prime the synapses for subsequent synapse-specific capture of L-LTP by a weak stimulus. Our analysis indicates that synaptic capture of CRE-driven gene products may be sufficient for consolidation of LTP and provides insight into the molecular mechanisms of synaptic tagging and synapse-specific potentiation.

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    • "Manipulation of CREB produces severe alterations in late phase-LTP (Bourtchuladze et al., 1994; Barco et al., 2002, 2005; Alarcon et al., 2004). Sleep loss for 8 h has been found to reduce the gene expression of CREB (Guzman-Marin et al., 2006). "
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    • "Unlike early-phase LTP, late phase LTP (L-LTP) requires gene expression and protein synthesis (Frey et al., 1993; Sweatt, 1999). The expression of L-LTP requires the participation of signalling molecules, including calcium/calmodulin kinase IV (CaMKIV) and mitogen-activated protein kinase/extracellular signal-related kinase, which phosphorylate cAMP response elementbinding protein (CREB) (Barco et al., 2002; Bramham & Messaoudi , 2005). The phosphorylated CREB (P-CREB) increases the expression of key target genes, including that encoding brainderived neurotrophic factor (BDNF), which, through activation of its tyrosine kinase B receptor, feeds back to regulate CREB activity, which, in turn, induces downstream structural and functional changes at the synaptic level. "
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    • "Such LTP that we called 'pharmacological' was compared to LTP induced by a single 100 Hz, 1 s train, the form that we described as 'electrical' E-LTP. From seven selected works (Winder et al., 1998; Barco et al., 2002; Woo and Nguyen, 2003; Kelleher et al., 2004; "
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