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Differential contributions of de novo and maintenance DNA methyltransferases to object memory processing in the rat hippocampus and perirhinal cortex – a double dissociation
Author(s) -
Mitchnick Krista A.,
Creighton Samantha,
O'Hara Matthew,
Kalisch Bettina E.,
Winters Boyer D.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12819
Subject(s) - perirhinal cortex , dna methyltransferase , methyltransferase , dentate gyrus , epigenetics , hippocampus , neuroscience , psychology , long term memory , downregulation and upregulation , dna methylation , chemistry , microbiology and biotechnology , biology , methylation , dna , recognition memory , biochemistry , gene expression , cognition , gene
Epigenetic mechanisms are increasingly acknowledged as major players in memory formation. Specifically, DNA methylation is necessary for the formation of long‐term memory in various brain regions, including the hippocampus ( HPC ); however, its role in the perirhinal cortex ( PR h), a structure critical for object memory, has not been characterized. Moreover, the mnemonic effects of selective DNA methyltransferase ( DNMT ) inhibition have not yet been investigated systematically, despite distinct roles for de novo ( DNMT 3a, 3b) and maintenance ( DNMT 1) methyltransferases. Consequently, we assessed the effects of various DNMT inhibitors within the HPC and PR h of rats using the object‐in‐place paradigm, which requires both brain regions. The non‐nucleoside DNA methyltransferase inhibitor RG ‐108 impaired long‐term object‐in‐place memory in both regions. Furthermore, intracranial administration of Accell short‐interference RNA sequences to inhibit the expression of individual DNMT s implicated DNMT 3a and DNMT 1 in the HPC and PR h effects, respectively. m RNA expression analyses revealed a complementary pattern of results, as only de novo DNMT 3a and DNMT 3b m RNA was upregulated in the HPC (dentate gyrus) following object‐in‐place learning, whereas DNMT 1 m RNA was selectively upregulated in the PR h. These results reinforce the established functional double dissociation between the HPC and PR h and imply the operation of different epigenetic mechanisms in brain regions dedicated to long‐term memory processing for different types of information.