Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0

Special Issue Editors
Special Issue Information
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 2022) | Viewed by 19687

Share This Special Issue

Special Issue Editor

Prof. Dr. Claudio Grassi

E-Mail Website
Guest Editor

Department of Neuroscience, Medical School, Università Cattolica del Sacro Cuore, Rome, Italy
Interests: molecular and cellular neuroscience; synaptic transmission and plasticity; neuronal excitability; neural stem cells and adult neurogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain functions rely on information encoding and its transmission within neural networks. As such, ion channels allowing the generation of electrical signals and governing neuronal excitability play a critical role in all physiological processes of central and peripheral nervous systems. Neuronal signaling also requires synaptic function to transmit information and allow elaboration of more complex responses in neural circuitries of the human brain. Of note, synaptic plasticity, i.e., changes in the synaptic strength, is pivotal for high-order processes such as learning and memory. Dysregulation of these physiological mechanisms controlling information encoding and its transmission, relying on ion channels, neurotransmitter receptors, and intracellular pathways regulating their expression and/or function, causes pathophysiological processes underlying major neuropsychiatric disorders. Therefore, the understanding of molecular and cellular mechanisms controlling neuronal excitability and synaptic function is fundamental for the insight into brain function and dysfunction. The scope of the Special Issue is to summarize and enhance knowledge in this field.

Authors are invited to submit original research, communications, and review articles which address the progress and current standing of neuronal excitability and synaptic function.

Topics include but are not limited to:

Ion channel function and their modulation;
Channelopathies;
Mechanisms governing neurotransmitter release;
Neurotransmitter receptors and transporters;
Altered synaptic function in neurological diseases;
Mechanistic links between candidate genes and brain disorders characterized by altered neuronal excitability and/or synaptic function.

Prof. Dr. Claudio Grassi
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.

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

36 pages, 5323 KiB

Open AccessArticle

Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum

by Laszlo G. Harsing, Joseph Knoll and Ildiko Miklya

Int. J. Mol. Sci. 2022, 23(15), 8543; https://doi.org/10.3390/ijms23158543 - 1 Aug 2022

Cited by 4 | Viewed by 2013

Abstract

The trace amine-associated receptor 1 (TAAR1) is a Gs protein-coupled, intracellularly located metabotropic receptor. Trace and classic amines, amphetamines, act as agonists on TAAR1; they activate downstream signal transduction influencing neurotransmitter release via intracellular phosphorylation. Our aim was to check the effect of the catecholaminergic activity enhancer compound ((−)BPAP, (R)-(−)-1-(benzofuran-2-yl)-2-propylaminopentane) on neurotransmitter release via the TAAR1 signaling. Rat striatal slices were prepared and the resting and electrical stimulation-evoked [³H]dopamine release was measured. The releaser (±)methamphetamine evoked non-vesicular [³H]dopamine release in a TAAR1-dependent manner, whereas (−)BPAP potentiated [³H]dopamine release with vesicular origin via TAAR1 mediation. (−)BPAP did not induce non-vesicular [³H]dopamine release. N-Ethylmaleimide, which inhibits SNARE core complex disassembly, potentiated the stimulatory effect of (−)BPAP on vesicular [³H]dopamine release. Subsequent analyses indicated that the dopamine-release stimulatory effect of (−)BPAP was due to an increase in PKC-mediated phosphorylation. We have hypothesized that there are two binding sites present on TAAR1, one for the releaser and one for the enhancer compounds, and they activate different PKC-mediated phosphorylation leading to the evoking of non-vesicular and vesicular dopamine release. (−)BPAP also increased VMAT2 operation enforcing vesicular [³H]dopamine accumulation and release. Vesicular dopamine release promoted by TAAR1 evokes activation of D2 dopamine autoreceptor-mediated presynaptic feedback inhibition. In conclusion, TAAR1 possesses a triggering role in both non-vesicular and vesicular dopamine release, and the mechanism of action of (−)BPAP is linked to the activation of TAAR1 and the signal transduction attached. Full article

(This article belongs to the Special Issue Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0)

► Show Figures

Graphical abstract

16 pages, 4065 KiB

Open AccessArticle

I_CAN (TRPM4) Contributes to the Intrinsic Excitability of Prefrontal Cortex Layer 2/3 Pyramidal Neurons

by Denise Riquelme, Francisco A. Peralta, Franco D. Navarro, Claudio Moreno and Elias Leiva-Salcedo

Int. J. Mol. Sci. 2021, 22(10), 5268; https://doi.org/10.3390/ijms22105268 - 17 May 2021

Cited by 5 | Viewed by 2804

Abstract

Pyramidal neurons in the medial prefrontal cortical layer 2/3 are an essential contributor to the cellular basis of working memory; thus, changes in their intrinsic excitability critically affect medial prefrontal cortex (mPFC) functional properties. Transient Receptor Potential Melastatin 4 (TRPM4), a calcium-activated nonselective cation channel (CAN), regulates the membrane potential in a calcium-dependent manner. In this study, we uncovered the role of TRPM4 in regulating the intrinsic excitability plasticity of pyramidal neurons in the mouse mPFC layer of 2/3 using a combination of conventional and nystatin perforated whole-cell recordings. Interestingly, we found that TRPM4 is open at resting membrane potential, and its inhibition increases input resistance and hyperpolarizes membrane potential. After high-frequency stimulation, pyramidal neurons increase a calcium-activated non-selective cation current, increase the action potential firing, and the amplitude of the afterdepolarization, these effects depend on intracellular calcium. Furthermore, pharmacological inhibition or genetic silencing of TRPM4 reduces the firing rate and the afterdepolarization after high frequency stimulation. Together, these results show that TRPM4 plays a significant role in the excitability of mPFC layer 2/3 pyramidal neurons by modulating neuronal excitability in a calcium-dependent manner. Full article

(This article belongs to the Special Issue Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 1662 KiB

Open AccessReview

Spinal Cord Injury and Loss of Cortical Inhibition

by Bruno Benedetti, Annika Weidenhammer, Maximilian Reisinger and Sebastien Couillard-Despres

Int. J. Mol. Sci. 2022, 23(10), 5622; https://doi.org/10.3390/ijms23105622 - 17 May 2022

Cited by 8 | Viewed by 3119

Abstract

After spinal cord injury (SCI), the destruction of spinal parenchyma causes permanent deficits in motor functions, which correlates with the severity and location of the lesion. Despite being disconnected from their targets, most cortical motor neurons survive the acute phase of SCI, and these neurons can therefore be a resource for functional recovery, provided that they are properly reconnected and retuned to a physiological state. However, inappropriate re-integration of cortical neurons or aberrant activity of corticospinal networks may worsen the long-term outcomes of SCI. In this review, we revisit recent studies addressing the relation between cortical disinhibition and functional recovery after SCI. Evidence suggests that cortical disinhibition can be either beneficial or detrimental in a context-dependent manner. A careful examination of clinical data helps to resolve apparent paradoxes and explain the heterogeneity of treatment outcomes. Additionally, evidence gained from SCI animal models indicates probable mechanisms mediating cortical disinhibition. Understanding the mechanisms and dynamics of cortical disinhibition is a prerequisite to improve current interventions through targeted pharmacological and/or rehabilitative interventions following SCI. Full article

(This article belongs to the Special Issue Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0)

► Show Figures

Graphical abstract

24 pages, 1401 KiB

Open AccessReview

Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases

by Mate Marosi, Parsa Arman, Giuseppe Aceto, Marcello D’Ascenzo and Fernanda Laezza

Int. J. Mol. Sci. 2022, 23(8), 4413; https://doi.org/10.3390/ijms23084413 - 16 Apr 2022

Cited by 10 | Viewed by 3905

Abstract

Glycogen synthase kinase 3β (GSK3) is a multifaceted serine/threonine (S/T) kinase expressed in all eukaryotic cells. GSK3β is highly enriched in neurons in the central nervous system where it acts as a central hub for intracellular signaling downstream of receptors critical for neuronal function. Unlike other kinases, GSK3β is constitutively active, and its modulation mainly involves inhibition via upstream regulatory pathways rather than increased activation. Through an intricate converging signaling system, a fine-tuned balance of active and inactive GSK3β acts as a central point for the phosphorylation of numerous primed and unprimed substrates. Although the full range of molecular targets is still unknown, recent results show that voltage-gated ion channels are among the downstream targets of GSK3β. Here, we discuss the direct and indirect mechanisms by which GSK3β phosphorylates voltage-gated Na⁺ channels (Na_v1.2 and Na_v1.6) and voltage-gated K⁺ channels (K_v4 and K_v7) and their physiological effects on intrinsic excitability, neuronal plasticity, and behavior. We also present evidence for how unbalanced GSK3β activity can lead to maladaptive plasticity that ultimately renders neuronal circuitry more vulnerable, increasing the risk for developing neuropsychiatric disorders. In conclusion, GSK3β-dependent modulation of voltage-gated ion channels may serve as an important pharmacological target for neurotherapeutic development. Full article

(This article belongs to the Special Issue Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0)

► Show Figures

Figure 1

17 pages, 636 KiB

Open AccessReview

Targeting Microglia-Synapse Interactions in Alzheimer’s Disease

by Gaia Piccioni, Dalila Mango, Amira Saidi, Massimo Corbo and Robert Nisticò

Int. J. Mol. Sci. 2021, 22(5), 2342; https://doi.org/10.3390/ijms22052342 - 26 Feb 2021

Cited by 30 | Viewed by 7057

Abstract

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be “resting” (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer’s disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer’s disease (AD) and other neurodegenerative disorders. Full article

(This article belongs to the Special Issue Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Modulation of Neuronal Excitability, Synaptic Transmission, and Plasticity in Health and Disease 2.0

Share This Special Issue

Special Issue Editor

Special Issue Information

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI