Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia.

Kaycey Pearce,Adam C Roberts,David L Glanzman,Diancai Cai

doi:10.7554/elife.18299

Kaycey Pearce, Adam C Roberts + Show 2 more

Open Access

https://doi.org/10.7554/elife.18299

Copy DOI

Journal: eLife	Publication Date: Jan 9, 2017
Citations: 64	License type: CC BY 4.0

Affiliation: University of California, Los Angeles

Abstract

Previously, we reported that long-term memory (LTM) in Aplysia can be reinstated by truncated (partial) training following its disruption by reconsolidation blockade and inhibition of PKM (Chen et al., 2014). Here, we report that LTM can be induced by partial training after disruption of original consolidation by protein synthesis inhibition (PSI) begun shortly after training. But when PSI occurs during training, partial training cannot subsequently establish LTM. Furthermore, we find that inhibition of DNA methyltransferase (DNMT), whether during training or shortly afterwards, blocks consolidation of LTM and prevents its subsequent induction by truncated training; moreover, later inhibition of DNMT eliminates consolidated LTM. Thus, the consolidation of LTM depends on two functionally distinct phases of protein synthesis: an early phase that appears to prime LTM; and a later phase whose successful completion is necessary for the normal expression of LTM. Both the consolidation and maintenance of LTM depend on DNA methylation.

Highlights

Since the pioneering work of the Flexners (Flexner et al, 1963), Agranoff (Agranoff and Klinger, 1964) and their colleagues, it has been widely accepted that memory consolidation—the process by which a labile, short-term memory trace is transformed into a stable, long-term trace (Lechner et al, 1999; Muller and Pilzecker, 1900)—requires protein synthesis (Davis and Squire, 1984; Goelet et al, 1986; Hernandez and Abel, 2008)
We have shown that protein synthesis during and shortly after sensitization training is essential for the normal consolidation of long-term memory (LTM) in Aplysia
We have significantly extended prior findings regarding protein synthesis and memory consolidation through our demonstration that LTM can be induced by supplemental partial training following its disruption by protein synthesis inhibition (PSI) shortly after the original long-term sensitization (LTS) training, but not following PSI during the original LTS training

Summary

Introduction

Since the pioneering work of the Flexners (Flexner et al, 1963), Agranoff (Agranoff and Klinger, 1964) and their colleagues, it has been widely accepted that memory consolidation—the process by which a labile, short-term memory trace is transformed into a stable, long-term trace (Lechner et al, 1999; Muller and Pilzecker, 1900)—requires protein synthesis (Davis and Squire, 1984; Goelet et al, 1986; Hernandez and Abel, 2008). Studies have classically observed significant disruptive effects on the consolidation of long-term memory (LTM) whether a protein synthesis inhibitor is applied either immediately prior to, or immediately after, training (e.g., Agranoff et al, 1966; Barondes and Cohen, 1968; Flexner and Flexner, 1968). Both early and late protein synthesis are commonly regarded as participating in a more-or-less unitary consolidative process. Protein synthesis is believed to mediate critical late events in memory consolidation, including late

Methods

Results

Conclusion