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Sustained CaMKII Delta Gene Expression Is Specifically Required for Long-Lasting Memories in Mice
Gisela Zalcman1,2, Noel Federman3, Ana Fiszbein2
1Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Molecular Neurobiology
|June 28, 2018
Summary
The calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ) isoform is crucial for long-lasting memory storage. Its sustained gene expression, regulated by epigenetic changes, underpins memory persistence in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Epigenetics
Background:
- Long-term memory formation mechanisms are known, but memory persistence processes remain unclear.
- Understanding how memories are maintained long-term is critical for neuroscience research.
Purpose of the Study:
- Investigate the role of the CaMKIIδ isoform in the persistence of long-lasting memories.
- Elucidate the molecular mechanisms, including gene expression and epigenetic regulation, underlying memory persistence.
Main Methods:
- Studied object recognition memory in mice.
- Measured CaMKIIδ mRNA expression levels post-training.
- Used antisense DNA infusion to inhibit CaMKIIδ.
- Analyzed nucleosome occupancy changes at the CaMKIIδ promoter.
Main Results:
- CaMKIIδ mRNA expression persisted for up to one week, correlating with memory retention.
- Inhibiting CaMKIIδ after memory consolidation impaired 7-day memory but not 1-day memory.
- Sustained CaMKIIδ gene expression was linked to long-lasting epigenetic changes (nucleosome occupancy) at its promoter.
Conclusions:
- Sustained CaMKIIδ gene expression, driven by epigenetic modifications, is essential for long-lasting memory persistence in the hippocampus.
- This study reveals a novel epigenetic mechanism for persistent gene expression in neurons relevant to memory.
- CaMKIIδ's nuclear and presynaptic localization suggests its role in these compartments for memory persistence.
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