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Neural Correlates and Molecular Mechanisms of Memory and Learning

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 (15 June 2023) | Viewed by 20108

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
1. Department of Psychology, University of Turin, Turin, Italy
2. Center for Studies and Research in Cognitive Neuroscience, Department of Psychology, University of Bologna, Bologna, Italy
Interests: NIBS techniques; TMS; skin conductance; heart rate variability; fear conditioning; fear learning; learning; neuropsychology; prefrontal cortex; amygdala; hippocampus; anxiety; depression; working memory; PTSD; skin conductance responses; psychophysiology; error-related negativity; EEG; tDCS; Alzheimer’s disease; PIT; stress-related disorders; Parkinson’s disease; resilience; memory; neurologic patients; cognitive decisions; fMRI; translational and molecular psychiatry
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged (MTA-SZTE), 6720 Szeged, Hungary
Interests: neurohormones; neuropeptides; tryptophan; kynurenine; psychiatry; neurology; depression; anxiety; dementia; cognition; antidepressant; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The neurobiological and molecular foundation of learning and memory is an issue that has attracted researchers for decades. Through the use of many different learning and memory paradigms in different organisms, we are beginning to have a deeper understanding of the molecular changes that allow neurons within the amygdala, the hippocampus, and prefrontal cortex, to create and store memories and improve learning.

The investigation of the biological basis of learning and memory requires a clear representation of molecular and cellular changes associated with brain plasticity, as memory formation depends on changes in synaptic efficiency that permit strengthening of associations between neurons. We also know that, at the cellular level, the storage of long-term memory is associated with gene expression, de novo protein synthesis, and the formation of new synaptic connections.

It has been suggested that long-term potentiation (LTP), a process by which strengthening of synaptic connections can be achieved, could be a valuable tool for studying the cellular and molecular mechanisms that occur in the different neural networks, involving the lateral amygdala, thalamus, visual cortex, and the prefrontal cortex, which are thought to be crucial in memory and learning formation.

This Special Issue welcomes original research or review articles focused on cellular and molecular evidence relating to different brain regions underlying memory and learning mechanisms.

Dr. Simone Battaglia
Dr. Masaru Tanaka
Guest Editors

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
  • synaptic plasticity
  • long-term potentiation
  • hippocampus
  • amygdala
  • prefrontal cortex

Published Papers (7 papers)

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Editorial

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11 pages, 275 KiB  
Editorial
Neural Correlates and Molecular Mechanisms of Memory and Learning
by Simone Battaglia, Alessio Avenanti, László Vécsei and Masaru Tanaka
Int. J. Mol. Sci. 2024, 25(5), 2724; https://doi.org/10.3390/ijms25052724 - 27 Feb 2024
Cited by 13 | Viewed by 3147
Abstract
Memory and learning are essential cognitive processes that enable us to obtain, retain, and recall information [...] Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)

Research

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17 pages, 2436 KiB  
Article
Multisensory Stimulation Reverses Memory Impairment in Adrβ3KO Male Mice
by Thaís T. Ravache, Alice Batistuzzo, Gabriela G. Nunes, Thiago G. B. Gomez, Fernanda B. Lorena, Bruna P. P. Do Nascimento, Maria Martha Bernardi, Eduarda R. R. Lima, Daniel O. Martins, Ana Carolina P. Campos, Rosana L. Pagano and Miriam O. Ribeiro
Int. J. Mol. Sci. 2023, 24(13), 10522; https://doi.org/10.3390/ijms241310522 - 23 Jun 2023
Cited by 3 | Viewed by 1298
Abstract
Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β1, β2 and β3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ3 (Adrβ3KO) with [...] Read more.
Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β1, β2 and β3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ3 (Adrβ3KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrβ3KO mice were exposed to an 8-week multisensory stimulation (MS) protocol that comprised gustatory and olfactory stimuli of positive and negative valence; intellectual challenges to reach food; the use of hidden objects; and the presentation of food in ways that prompted foraging, which was followed by analysis of GFAP, Iba-1 and EAAT2 protein expression in the hippocampus (HC) and amygdala (AMY). The MS protocol reduced GFAP and Iba-1 expression in the HC of young mice but not in older mice. While this protocol restored memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrβ3KO mice. In the AMY of Adrβ3KO older mice, we observed an increase in GFAP and EAAT2 expression when compared to wild-type (WT) mice that MS was unable to reduce. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied immediately after weaning in Adrβ3KO animals and indicates that the control of neuroinflammation mediates this response. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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12 pages, 1453 KiB  
Article
Recognition Memory Induces Natural LTP-like Hippocampal Synaptic Excitation and Inhibition
by Irene Sánchez-Rodríguez, Sara Temprano-Carazo, Danko Jeremic, Jose Maria Delgado-Garcia, Agnès Gruart, Juan D. Navarro-López and Lydia Jiménez-Díaz
Int. J. Mol. Sci. 2022, 23(18), 10806; https://doi.org/10.3390/ijms231810806 - 16 Sep 2022
Cited by 10 | Viewed by 2141
Abstract
Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic [...] Read more.
Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3–CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABAA-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3–CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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17 pages, 3178 KiB  
Article
Effects of RU486 in Treatment of Traumatic Stress-Induced Glucocorticoid Dysregulation and Fear-Related Abnormalities: Early versus Late Intervention
by Chen-Cheng Lin, Pao-Yun Cheng, Michael Hsiao and Yia-Ping Liu
Int. J. Mol. Sci. 2022, 23(10), 5494; https://doi.org/10.3390/ijms23105494 - 14 May 2022
Cited by 15 | Viewed by 2808
Abstract
Central glucocorticoid receptor (GR) activity is enhanced following traumatic events, playing a key role in the stress-related cognitive abnormalities of posttraumatic stress disorder (PTSD). GR antagonists are expected to have potential as pharmacological agents to treat PTSD-related symptoms such as anxiety and fear [...] Read more.
Central glucocorticoid receptor (GR) activity is enhanced following traumatic events, playing a key role in the stress-related cognitive abnormalities of posttraumatic stress disorder (PTSD). GR antagonists are expected to have potential as pharmacological agents to treat PTSD-related symptoms such as anxiety and fear memory disruption. However, an incubation period is usually required and stress-induced abnormalities do not develop immediately following the trauma; thus, the optimal intervention timing should be considered. Single prolonged stress (SPS) was employed as a rodent PTSD model to examine the effects of early or late (1–7 versus 8–14 days after the SPS) sub-chronic RU486 (a GR antagonist) administration. Behaviorally, fear conditioning and anxiety behavior were assessed using the fear-conditioning test and elevated T-maze (ETM), respectively. Neurochemically, the expressions of GR, FK506-binding proteins 4 and 5 (FKBP4 and FKBP5), and early growth response-1 (Egr-1) were assessed in the hippocampus, medial prefrontal cortex (mPFC), amygdala, and hypothalamus, together with the level of plasma corticosterone. Early RU486 administration could inhibit SPS-induced behavioral abnormalities and glucocorticoid system dysregulation by reversing the SPS-induced fear extinction deficit, and preventing SPS-reduced plasma corticosterone levels and SPS-induced Egr-1 overexpression in the hippocampus. Early RU486 administration following SPS also increased the FKBP5 level in the hippocampus and hypothalamus. Finally, both early and late RU486 administration inhibited the elevated hippocampal FKBP4 level and hypothalamus GR level in the SPS rats. Early intervention with a GR antagonist aids in the correction of traumatic stress-induced fear and anxiety dysregulation. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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29 pages, 6802 KiB  
Article
Phasic Dopamine Changes and Hebbian Mechanisms during Probabilistic Reversal Learning in Striatal Circuits: A Computational Study
by Miriam Schirru, Florence Véronneau-Veilleux, Fahima Nekka and Mauro Ursino
Int. J. Mol. Sci. 2022, 23(7), 3452; https://doi.org/10.3390/ijms23073452 - 22 Mar 2022
Cited by 8 | Viewed by 2949
Abstract
Cognitive flexibility is essential to modify our behavior in a non-stationary environment and is often explored by reversal learning tasks. The basal ganglia (BG) dopaminergic system, under a top-down control of the pre-frontal cortex, is known to be involved in flexible action selection [...] Read more.
Cognitive flexibility is essential to modify our behavior in a non-stationary environment and is often explored by reversal learning tasks. The basal ganglia (BG) dopaminergic system, under a top-down control of the pre-frontal cortex, is known to be involved in flexible action selection through reinforcement learning. However, how adaptive dopamine changes regulate this process and learning mechanisms for training the striatal synapses remain open questions. The current study uses a neurocomputational model of the BG, based on dopamine-dependent direct (Go) and indirect (NoGo) pathways, to investigate reinforcement learning in a probabilistic environment through a task that associates different stimuli to different actions. Here, we investigated: the efficacy of several versions of the Hebb rule, based on covariance between pre- and post-synaptic neurons, as well as the required control in phasic dopamine changes crucial to achieving a proper reversal learning. Furthermore, an original mechanism for modulating the phasic dopamine changes is proposed, assuming that the expected reward probability is coded by the activity of the winner Go neuron before a reward/punishment takes place. Simulations show that this original formulation for an automatic phasic dopamine control allows the achievement of a good flexible reversal even in difficult conditions. The current outcomes may contribute to understanding the mechanisms for active control of dopamine changes during flexible behavior. In perspective, it may be applied in neuropsychiatric or neurological disorders, such as Parkinson’s or schizophrenia, in which reinforcement learning is impaired. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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Review

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26 pages, 1744 KiB  
Review
Neuropharmacological Modulation of N-methyl-D-aspartate, Noradrenaline and Endocannabinoid Receptors in Fear Extinction Learning: Synaptic Transmission and Plasticity
by Simone Battaglia, Chiara Di Fazio, Carmelo M. Vicario and Alessio Avenanti
Int. J. Mol. Sci. 2023, 24(6), 5926; https://doi.org/10.3390/ijms24065926 - 21 Mar 2023
Cited by 43 | Viewed by 4150
Abstract
Learning to recognize and respond to potential threats is crucial for survival. Pavlovian threat conditioning represents a key paradigm for investigating the neurobiological mechanisms of fear learning. In this review, we address the role of specific neuropharmacological adjuvants that act on neurochemical synaptic [...] Read more.
Learning to recognize and respond to potential threats is crucial for survival. Pavlovian threat conditioning represents a key paradigm for investigating the neurobiological mechanisms of fear learning. In this review, we address the role of specific neuropharmacological adjuvants that act on neurochemical synaptic transmission, as well as on brain plasticity processes implicated in fear memory. We focus on novel neuropharmacological manipulations targeting glutamatergic, noradrenergic, and endocannabinoid systems, and address how the modulation of these neurobiological systems affects fear extinction learning in humans. We show that the administration of N-methyl-D-aspartate (NMDA) agonists and modulation of the endocannabinoid system by fatty acid amide hydrolase (FAAH) inhibition can boost extinction learning through the stabilization and regulation of the receptor concentration. On the other hand, elevated noradrenaline levels dynamically modulate fear learning, hindering long-term extinction processes. These pharmacological interventions could provide novel targeted treatments and prevention strategies for fear-based and anxiety-related disorders. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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Other

8 pages, 791 KiB  
Case Report
Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report
by Roberto De Masi, Stefania Orlando, Vincenzo Toni and Maria Carmela Costa
Int. J. Mol. Sci. 2023, 24(3), 2968; https://doi.org/10.3390/ijms24032968 - 3 Feb 2023
Cited by 4 | Viewed by 1692
Abstract
We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven [...] Read more.
We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances. Despite bio-humoral and instrumental investigations and DaTScan were negative, MRI post-analysis evidenced a 6.5% loss in brain volume. Specifically, irreversible cortical and sub-cortical grey matter reduction and cerebrospinal fluid space enlargement with spared white matter were found. Our observations suggest that the sudden availability of Fluphenazine results in a kind of plateau effect of parkinsonism presentation, partially reversible due to the neurotoxic drug effect on the cortical and sub-cortical grey matter, resulting in asymmetric EPS and stable memory loss, respectively. Our report confirms the debated neurotoxicity of first-generation neuroleptics and the postulated theory of differential susceptibility to the cytotoxic stressors on the central nervous system. Full article
(This article belongs to the Special Issue Neural Correlates and Molecular Mechanisms of Memory and Learning)
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