scholarly journals CREBA and CREBB in two identified neurons gate long-term memory formation in Drosophila

2021 ◽  
Vol 118 (37) ◽  
pp. e2100624118
Author(s):  
Hsuan-Wen Lin ◽  
Chun-Chao Chen ◽  
J. Steven de Belle ◽  
Tim Tully ◽  
Ann-Shyn Chiang

Episodic events are frequently consolidated into labile memory but are not necessarily transferred to persistent long-term memory (LTM). Regulatory mechanisms leading to LTM formation are poorly understood, however, especially at the resolution of identified neurons. Here, we demonstrate enhanced LTM following aversive olfactory conditioning in Drosophila when the transcription factor cyclic AMP response element binding protein A (CREBA) is induced in just two dorsal-anterior-lateral (DAL) neurons. Our experiments show that this process is regulated by protein–gene interactions in DAL neurons: (1) crebA transcription is induced by training and repressed by crebB overexpression, (2) CREBA bidirectionally modulates LTM formation, (3) crebA overexpression enhances training-induced gene transcription, and (4) increasing membrane excitability enhances LTM formation and gene expression. These findings suggest that activity-dependent gene expression in DAL neurons during LTM formation is regulated by CREB proteins.

2012 ◽  
Vol 2 (11) ◽  
pp. 1437-1445 ◽  
Author(s):  
Ari Winbush ◽  
Danielle Reed ◽  
Peter L. Chang ◽  
Sergey V. Nuzhdin ◽  
Lisa C. Lyons ◽  
...  

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Snehajyoti Chatterjee ◽  
Christopher C. Angelakos ◽  
Ethan Bahl ◽  
Joshua D. Hawk ◽  
Marie E. Gaine ◽  
...  

Abstract Background CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. Results We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. Conclusions These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms. Graphical abstract


Cell ◽  
2002 ◽  
Vol 111 (4) ◽  
pp. 483-493 ◽  
Author(s):  
Zhonghui Guan ◽  
Maurizio Giustetto ◽  
Stavros Lomvardas ◽  
Joung-Hun Kim ◽  
Maria Concetta Miniaci ◽  
...  

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Vivek Sagar ◽  
Thorsten Kahnt

Memorable positive and negative experiences produce different profiles of gene expression in brain areas associated with long-term memory.


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.


Cell ◽  
1994 ◽  
Vol 79 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Roussoudan Bourtchuladze ◽  
Bruno Frenguelli ◽  
Julie Blendy ◽  
Diana Cioffi ◽  
Gunther Schutz ◽  
...  

2020 ◽  
Author(s):  
Snehajyoti Chatterjee ◽  
Christopher C. Angelakos ◽  
Ethan Bahl ◽  
Joshua D. Hawk ◽  
Marie E. Gaine ◽  
...  

AbstractCREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIX mice. With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.


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