Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein

Cell ◽  
1994 ◽  
Vol 79 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Roussoudan Bourtchuladze ◽  
Bruno Frenguelli ◽  
Julie Blendy ◽  
Diana Cioffi ◽  
Gunther Schutz ◽  
...  
2006 ◽  
Vol 26 (23) ◽  
pp. 9105-9115 ◽  
Author(s):  
Frank Blaeser ◽  
Matthew J. Sanders ◽  
Nga Truong ◽  
Shanelle Ko ◽  
Long Jun Wu ◽  
...  

ABSTRACT Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKα mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKα mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKα in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.


2001 ◽  
Vol 21 (7) ◽  
pp. 2404-2412 ◽  
Author(s):  
Sheena A. Josselyn ◽  
Chanjun Shi ◽  
William A. Carlezon ◽  
Rachael L. Neve ◽  
Eric J. Nestler ◽  
...  

1998 ◽  
Vol 6 (3) ◽  
pp. 63-68 ◽  
Author(s):  
Pascal Roullet ◽  
Susan Sara

Evidence is growing that the cAMP pathway through the cAMP responsive element binding protein (CREB) transcription factor plays an important role in long-term memory formation (LTM). To study the role of ß-noradrenergic receptors, positively linked to the cAMP secondmessenger system, in the dynamics of LTM processes, we used a memory-reactivation paradigm because recent studies in our laboratory confirmed that reactivated memory is labile and undergoes an extended reconsolidation process. In an eight-arm maze, rats were trained to choose the same three baited arms; 24 hr later, memory was reactivated and then the rats were injected intracerebroventricularly at 5 min, 30 min, 60 min, or 5 hr later with the ß-antagonist timolol or with saline. The results showed that injection of timolol induced amnesia only at the 60 min post-reactivation interval, whereas all control groups and groups that were timolol-injected at other post-reactivation intervals displayed optimal retention. The delayed amnesic action of timoloi suggests that ß noradrenergic receptors and the cAMP cascade are implicated in the late phase of reprocessing of a remembered event.


Author(s):  
Lenzie Ford ◽  
Arun Asok ◽  
Arielle D. Tripp ◽  
Cameron Parro ◽  
Michelle Fitzpatrick ◽  
...  

SummaryBiomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs), a type of biomolecular condensate found in neurons that are necessary for local protein synthesis and are involved in long-term potentiation (LTP). Several RNA-binding proteins present in RNPs are necessary for the synaptic plasticity involved in LTP and long-term memory. Most of these proteins possess low complexity motifs, allowing for increased promiscuity. We explore the role the low complexity motif plays for RNA binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3), a protein necessary for long-term memory persistence. We found that RNA binding and SUMOylation are necessary for CPEB3 localization to the P body, thereby having functional implications on translation. Here, we investigate the role of the low complexity motif of CPEB3 and find that it is necessary for P body localization and downstream targeting for local protein synthesis.


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