LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation
Language: 
English
Abstract: 

One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling. The binding of Reelin to its receptor, LRP8, triggers activation of this cohort of LRP8-Reelin-regulated neuronal (LRN) enhancers that serve as the ultimate convergence point of a novel synapse-to-nucleus pathway. Reelin simultaneously regulates NMDA-receptor transmission, which reciprocally permits the required ?-secretase-dependent cleavage of LRP8, revealing an unprecedented role for its intracellular domain in the regulation of synaptically generated signals. These results uncover an in vivo enhancer code serving as a critical molecular component of cognition and relevant to psychiatric disorders linked to defects in Reelin signaling.

Author(s): 
Telese, Francesca
Ma, Qi
Perez, Patricia Montilla
Notani, Dimple
Oh, Soohwan
Li, Wenbo
Comoletti, Davide
Ohgi, Kenneth A.
Taylor, Havilah
Rosenfeld, Michael G.
Item Type: 
Journal Article
Publication Title: 
Neuron
Journal Abbreviation: 
Neuron
Publication Date: 
5/6/2015
Publication Year: 
2015
Pages: 
696-710
Volume: 
86
Issue: 
3
ISSN: 
1097-4199
DOI: 
10.1016/j.neuron.2015.03.033
Library Catalog: 
PubMed
Extra: 
PMID: 25892301 PMCID: PMC4486257

Turabian/Chicago Citation

Francesca Telese, Qi Ma, Patricia Montilla Perez, Dimple Notani, Soohwan Oh, Wenbo Li, Davide Comoletti, Kenneth A. Ohgi, Havilah Taylor and Michael G. Rosenfeld. 5/6/2015. "LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation." Neuron 86: 3: 696-710. 10.1016/j.neuron.2015.03.033.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.neuron.2015.03.033 | issn = 1097-4199 | volume = 86 | pages = 696-710 | last = Telese | first = Francesca | coauthors = Ma, Qi, Perez, Patricia Montilla, Notani, Dimple, Oh, Soohwan, Li, Wenbo, Comoletti, Davide, Ohgi, Kenneth A., Taylor, Havilah, Rosenfeld, Michael G. | title = LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation | journal = Neuron | date = 5/6/2015 | pmid = | pmc = }} </ref>