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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: 33.12). 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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Available from: Angel Barco, Aug 19, 2015
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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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    ABSTRACT: Long-term potentiation (LTP) remains the most widely accepted model for learning and memory. In accordance with this belief, the temporal differentiation of LTP into early and late phases is accepted as reflecting the differentiation of short-term and long-term memory. Moreover, during the past 30 years, protein synthesis inhibitors have been used to separate the early, protein synthesis-independent (E-LTP) phase and the late, protein synthesis-dependent (L-LTP) phase. However, the role of these proteins has not been formally identified. Additionally, several reports failed to show an effect of protein synthesis inhibitors on LTP. In this review, a detailed analysis of extensive behavioral and electrophysiological data reveals that the presumed correspondence of LTP temporal phases to memory phases is neither experimentally nor theoretically consistent. Moreover, an overview of the time courses of E-LTP in hippocampal slices reveals a wide variability ranging from <1 h to more than 5 h. The existence of all these conflictual findings should lead to a new vision of LTP. We believe that the E-LTP vs. L-LTP distinction, established with protein synthesis inhibitor studies, reflects a false dichotomy. We suggest that the duration of LTP and its dependency on protein synthesis are related to the availability of a set of proteins at synapses and not to the de novo synthesis of plasticity-related proteins. This availability is determined by protein turnover kinetics, which is regulated by previous and ongoing electrical activities and by energy store availability.
    Reviews in the neurosciences 05/2015; DOI:10.1515/revneuro-2014-0072 · 3.31 Impact Factor
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    • "These pathways are established as essential for LTP. PKA phosphorylation of an unspecified substrate is necessary to set a synaptic tag required for synaptic " capture " of proteins necessary for late LTP (Barco et al., 2002; Frey and Morris, 1997; Redondo and Morris, 2011). This PKA-sensitive synaptic tag is denoted Tag-2 (Fig. 1). "
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    • "Thus, activation of either receptor will lead to a phosphorylation processes, albeit possibly of different proteins. The two signaling cascades converge ultimately on a common pathway involving the transcription factor, CREB (cAMP response element-binding protein) that supports long-term synaptic plasticity in the hippocampus [45]. "
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