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Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting.

ABSTRACT: Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference. To determine the role of CaMKII and GluA1 in adaptive forgetting, we adopted a comparative approach to assess the relative quantity and phosphorylation state of these proteins in the brain of rats trained in one of three radial maze paradigms: a RM task, a WM task involving a high level of adaptive forgetting, or a WM involving a low level of adaptive forgetting. Surprisingly, Western blot analyses revealed that training in a WM task involving a high level of adaptive forgetting specifically increased the expression of AMPA receptor GluA1 subunit and the activity of CaMKII in the dentate gyrus. These results highlight that WM with proactive interference involves mechanisms of synaptic plasticity selectively in the dentate gyrus.

SUBMITTER: Fraize N

PROVIDER: S-EPMC5238719 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting.

Fraize Nicolas N Hamieh Al Mahdy AM Joseph Mickaël Antoine MA Touret Monique M Parmentier Régis R Salin Paul Antoine PA Malleret Gaël G

Learning & memory (Cold Spring Harbor, N.Y.) 20170117 2

Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones t ...[more]

PMID: 28096498

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Project description:BackgroundBinge Drinking (BD) has been associated with altered inhibitory control and augmented alcohol-cue reactivity. Memory inhibition (MI), the ability to voluntarily suppress unwanted thoughts/memories, may lead to forgetting of memories in several psychiatric conditions. However, despite its potential clinical implications, no study to date has explored the MI abilities in populations with substance misuse, such as binge drinkers (BDs).MethodThis study-registered in the NIH Clinical Trials Database (ClinicalTrials.gov identifier: NCT05237414)-aims firstly to examine the behavioral and electroencephalographic (EEG) correlates of MI among college BDs. For this purpose, 45 BDs and 45 age-matched non/low-drinkers (50% female) will be assessed by EEG while performing the Think/No-Think Alcohol task, a paradigm that evaluates alcohol-related MI. Additionally, this work aims to evaluate an alcohol-specific MI intervention protocol using cognitive training (CT) and transcranial direct current stimulation (tDCS) while its effects on behavioral and EEG outcomes are assessed. BDs will be randomly assigned to one MI training group: combined [CT and verum tDCS applied over the right dorsolateral prefrontal cortex (DLPFC)], cognitive (CT and sham tDCS), or control (sham CT and sham tDCS). Training will occur in three consecutive days, in three sessions. MI will be re-assessed in BDs through a post-training EEG assessment. Alcohol use and craving will be measured at the first EEG assessment, and both 10-days and 3-months post-training. In addition, behavioral and EEG data will be collected during the performance of an alcohol cue reactivity (ACR) task, which evaluates attentional bias toward alcoholic stimuli, before, and after the MI training sessions.DiscussionThis study protocol will provide the first behavioral and neurofunctional MI assessment in BDs. Along with poor MI abilities, BDs are expected to show alterations in event-related potentials and functional connectivity patterns associated with MI. Results should also demonstrate the effectiveness of the protocol, with BDs exhibiting an improved capacity to suppress alcohol-related memories after both combined and cognitive training, along with a reduction in alcohol use and craving in the short/medium-term. Collectively, these findings might have major implications for the understanding and treatment of alcohol misuse.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT05237414].

Dataset Information

Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting.

Publications

Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting.

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