Epigenetics edit
Early theories, in 1969 and 1999, on the molecular basis of memory proposed that addition of a methyl group to particular cytosines in DNA of neurons (epigenetic alterations) could be the basis of memory.[1][2] In 2007, Miller and Sweatt[3] first experimentally explored the role of cytosine methylation in memory formation. They found that DNA methylation levels are rapidly and dynamically regulated in the rat brain hippocampus following formation of a new strong memory due to contextual fear conditioning. By 2015 it had become clear that long-term memory requires gene transcription activation and de novo protein synthesis in neurons,[4] and that activation and repression of genes during memory formation was controlled in large part by DNA methylation/DNA demethylation .[5]
When a new, strong, long-term memory is created in rats through contexual fear conditioning, those rats can have reduced expression of roughly 1,000 genes and increased expression of roughly 500 genes in the hippocampus at a time-point 24 hours after training. In total, this reflects altered expression of about 9% of the rat hippocampal genome. Reduced expression of genes was associated with methylation of the genes.[6]
As shown in 2019, the neuronal genes that had methylation-controlled increases or decreases in transcription then had their induced messenger RNAs (mRNAs) transported by neural granules (messenger RNPs) to the dendritic spines, where synapses are formed. At these locations the mRNAs can be translated into the proteins that control signaling at neuronal synapses.[7]
- ^ Griffith JS, Mahler HR (August 1969). "DNA ticketing theory of memory". Nature. 223 (5206): 580–2. doi:10.1038/223580a0. PMID 5799529.
- ^ Holliday R (October 1999). "Is there an epigenetic component in long-term memory?". J Theor Biol. 200 (3): 339–41. doi:10.1006/jtbi.1999.0995. PMID 10527722.
- ^ Miller CA, Sweatt JD (March 2007). "Covalent modification of DNA regulates memory formation". Neuron. 53 (6): 857–69. doi:10.1016/j.neuron.2007.02.022. PMID 17359920.
- ^ Alberini CM, Kandel ER (December 2014). "The regulation of transcription in memory consolidation". Cold Spring Harb Perspect Biol. 7 (1): a021741. doi:10.1101/cshperspect.a021741. PMC 4292167. PMID 25475090.
- ^ Oliveira AM (October 2016). "DNA methylation: a permissive mark in memory formation and maintenance". Learn Mem. 23 (10): 587–93. doi:10.1101/lm.042739.116. PMC 5026210. PMID 27634149.
- ^ Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD (July 2017). "Experience-dependent epigenomic reorganization in the hippocampus". Learn Mem. 24 (7): 278–288. doi:10.1101/lm.045112.117. PMC 5473107. PMID 28620075.
- ^ Bauer KE, Segura I, Gaspar I, Scheuss V, Illig C, Ammer G, Hutten S, Basyuk E, Fernández-Moya SM, Ehses J, Bertrand E, Kiebler MA (July 2019). "Live cell imaging reveals 3'-UTR dependent mRNA sorting to synapses". Nat Commun. 10 (1): 3178. doi:10.1038/s41467-019-11123-x. PMC 6639396. PMID 31320644.