Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 8399

Share This Special Issue

Special Issue Editor

Prof. Dr. Efthimios M. C. Skoulakis

E-Mail Website
Guest Editor

Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center “Alexander Fleming”, 16672 Vari, Greece
Interests: mechanisms of habituation; associative learning and memory in Drosophila and mice; pharmacogenetics of neurodegenerative tauopathies; learning disabilities and psychiatric conditions in Drosophila models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Learning and memory are sub-served by distinct processes, such as encoding, consolidation storage, retrieval and the modulation of the mnemonic engram. Although the cellular and molecular events underlying these processes have been extensively studied, the precise mechanisms differentiating them and the neural codes employed are currently, at best, fragmentary.

The circuitry and molecular mechanisms potentially differentially engaged, and hence characterizing distinct types of learning and memory forms (e.g., episodic, emotional, procedural, working, and non-associative), are little understood to date. The role of neuronal population oscillatory dynamics, the orchestration of activities of different neurotransmitters and neuromodulators—including the effects of stress or gonadal hormones—the intracellular signaling pathways engaged, or the epigenetic and epitranscriptomic modifications imposed by learning and being connected with memory have been intensely studied, but much remains unexplored.

We invite contributions of original research papers, computational models, and reviews, as well as position/theoretical papers. Studies combining experimental approaches, including genetic/epigenetic interventions, cellular, biochemical, molecular, -omics analyses, optogenetic manipulations or behavioral assays, are encouraged. Reviews and position/theoretical papers addressing these themes in a comparative approach, across memory types, neuronal modalities or experimental species, are welcome.

Prof. Dr. Efthimios M.C. Skoulakis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

learning
memory
neuronal
neurotransmitters
neuromodulators
epigenetic
epitranscriptomic modifications

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

20 pages, 2871 KiB

Open AccessArticle

Inhibition of ERK1/2 or CRMP2 Disrupts Alcohol Memory Reconsolidation and Prevents Relapse in Rats

by Nofar Rahamim, Mirit Liran, Coral Aronovici, Hila Flumin, Tamar Gordon, Nataly Urshansky and Segev Barak

Int. J. Mol. Sci. 2024, 25(10), 5478; https://doi.org/10.3390/ijms25105478 - 17 May 2024

Viewed by 249

Abstract

Relapse to alcohol abuse, often caused by cue-induced alcohol craving, is a major challenge in alcohol addiction treatment. Therefore, disrupting the cue-alcohol memories can suppress relapse. Upon retrieval, memories transiently destabilize before they reconsolidate in a process that requires protein synthesis. Evidence suggests that the mammalian target of rapamycin complex 1 (mTORC1), governing the translation of a subset of dendritic proteins, is crucial for memory reconsolidation. Here, we explored the involvement of two regulatory pathways of mTORC1, phosphoinositide 3-kinase (PI3K)-AKT and extracellular regulated kinase 1/2 (ERK1/2), in the reconsolidation process in a rat (Wistar) model of alcohol self-administration. We found that retrieval of alcohol memories using an odor-taste cue increased ERK1/2 activation in the amygdala, while the PI3K-AKT pathway remained unaffected. Importantly, ERK1/2 inhibition after alcohol memory retrieval impaired alcohol-memory reconsolidation and led to long-lasting relapse suppression. Attenuation of relapse was also induced by post-retrieval administration of lacosamide, an inhibitor of collapsin response mediator protein-2 (CRMP2)—a translational product of mTORC1. Together, our findings indicate the crucial role of ERK1/2 and CRMP2 in the reconsolidation of alcohol memories, with their inhibition as potential treatment targets for relapse prevention. Full article

(This article belongs to the Special Issue Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0)

► Show Figures

Figure 1

19 pages, 4444 KiB

Open AccessArticle

Fear Conditioning by Proxy: The Role of High Affinity Nicotinic Acetylcholine Receptors

by Zinovia Stavroula Chalkea, Danai Papavranoussi-Daponte, Alexia Polissidis, Marinos Kampisioulis, Marina Pagaki-Skaliora, Eleni Konsolaki and Irini Skaliora

Int. J. Mol. Sci. 2023, 24(20), 15143; https://doi.org/10.3390/ijms242015143 - 13 Oct 2023

Viewed by 1207

Abstract

Observational fear-learning studies in genetically modified animals enable the investigation of the mechanisms underlying the social transmission of fear-related information. Here, we used a three-day protocol to examine fear conditioning by proxy (FCbP) in wild-type mice (C57BL/6J) and mice lacking the β2-subunit of the nicotinic acetylcholine receptor (nAChR). Male animals of both genotypes were exposed to a previously fear-conditioned (FC) cage mate during the presentation of the conditioned stimulus (CS, tone). On the following day, observer (FCbP) mice were tested for fear reactions to the tone: none of the β2-KO mice froze to the stimulus, while 30% of the wild-type mice expressed significant freezing. An investigation of the possible factors that predicted the fear response revealed that only wild-type mice that exhibited enhanced and more flexible social interaction with the FC cage mate during tone presentations (Day 2) expressed fear toward the CS (Day-3). Our results indicate that (i) FCbP is possible in mice; (ii) the social transmission of fear depends on the interaction pattern between animals during the FCbP session and (iii) β2-KO mice display a more rigid interaction pattern compared to wild-type mice and are unable to acquire such information. These data suggest that β2-nAChRs influence observational fear learning indirectly through their effect on social behaviour. Full article

(This article belongs to the Special Issue Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0)

► Show Figures

Figure 1

32 pages, 5373 KiB

Open AccessArticle

Secreted Amyloid Precursor Protein Alpha (sAPPα) Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes

by Katie Peppercorn, Torsten Kleffmann, Stephanie M. Hughes and Warren P. Tate

Int. J. Mol. Sci. 2023, 24(8), 7165; https://doi.org/10.3390/ijms24087165 - 12 Apr 2023

Cited by 2 | Viewed by 1670

Abstract

Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer’s disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation. Full article

(This article belongs to the Special Issue Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0)

► Show Figures

Figure 1

20 pages, 3644 KiB

Open AccessArticle

Differential Effects of Human Tau Isoforms to Neuronal Dysfunction and Toxicity in the Drosophila CNS

by Ergina Vourkou, Vassilis Paspaliaris, Anna Bourouliti, Maria-Christina Zerva, Engie Prifti, Katerina Papanikolopoulou and Efthimios M. C. Skoulakis

Int. J. Mol. Sci. 2022, 23(21), 12985; https://doi.org/10.3390/ijms232112985 - 26 Oct 2022

Cited by 4 | Viewed by 2090

Abstract

Accumulation of highly post-translationally modified tau proteins is a hallmark of neurodegenerative disorders known as tauopathies, the most common of which is Alzheimer’s disease. Although six tau isoforms are found in the human brain, the majority of animal and cellular tauopathy models utilize a representative single isoform. However, the six human tau isoforms present overlapping but distinct distributions in the brain and are differentially involved in particular tauopathies. These observations support the notion that tau isoforms possess distinct functional properties important for both physiology and pathology. To address this hypothesis, the six human brain tau isoforms were expressed singly in the Drosophila brain and their effects in an established battery of assays measuring neuronal dysfunction, vulnerability to oxidative stress and life span were systematically assessed comparatively. The results reveal isoform-specific effects clearly not attributed to differences in expression levels but correlated with the number of microtubule-binding repeats and the accumulation of a particular isoform in support of the functional differentiation of these tau isoforms. Delineation of isoform-specific effects is essential to understand the apparent differential involvement of each tau isoform in tauopathies and their contribution to neuronal dysfunction and toxicity. Full article

(This article belongs to the Special Issue Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

23 pages, 2075 KiB

Open AccessReview

Epigenetic Changes and Chromatin Reorganization in Brain Function: Lessons from Fear Memory Ensemble and Alzheimer’s Disease

by Brigitte van Zundert and Martin Montecino

Int. J. Mol. Sci. 2022, 23(20), 12081; https://doi.org/10.3390/ijms232012081 - 11 Oct 2022

Cited by 7 | Viewed by 2716

Abstract

Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the last three decades demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Recent genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact with upregulated gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer–promoter interactions (EPIs) is critical if we are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. Here, we overview relevant discoveries in the field supporting the role of the chromatin organization and of specific epigenetic mechanisms during the control of gene transcription in neural cells from healthy mice subjected to the fear conditioning paradigm, a relevant model to study memory ensemble. Additionally, special consideration is dedicated to revising recent results generated by investigators working with animal models and human postmortem brain tissue to address how changes in the epigenome and chromatin architecture contribute to transcriptional dysregulation in Alzheimer’s disease, a widely studied neurodegenerative disease. We also discuss recent developments of potential new therapeutic strategies involving epigenetic editing and small chromatin-modifying molecules (or epidrugs). Full article

(This article belongs to the Special Issue Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory 2.0)

► Show Figures