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Biomedicines
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Synaptic Transmission: From Molecular to Neural Network Levels
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Synaptic Transmission: From Molecular to Neural Network Levels

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 11746

Special Issue Editors

Dr. Simona Tritto

E-Mail Website
Guest Editor
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
Interests: neurophysiology; cerebellum; synaptic plasticity; neurotransmission; optogenetics; brain modelling
Special Issues, Collections and Topics in MDPI journals
Dr. Lisa Mapelli

E-Mail Website
Guest Editor
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
Interests: neurophysiology; cerebellum; synaptic plasticity; neurotransmission; optogenetics; NMDA receptors; autism mouse models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The communication between neurons is at the foundation of every neurophysiological activity, such as sensory perception, learning, and memory. It is well known that in the central nervous system, the number of neurons is around 1012, and the number of synapses can reach a thousand billion. This anatomical complexity is heightened by the complexity of mechanisms underlying synaptic transmission. Every connection adds processing features to the network activity, originating an ensemble that shows emerging properties that are difficult to track back to the single synapse level. Here comes the need for both bottom-up and top-down approaches to understand brain activity: how do the different components of neural machinery interact to generate such complex systems? How can the understanding of new pathways be used for pathologies’ treatments? Investigations at these two levels are both needed to reach a comprehensive view of brain activity. While the microscale level has often been the leading actor of neuroscience research, the mesoscale-to-macroscale level has attracted more and more attention in the last decade.

This Special Issue aims to provide a broad picture of the latest discoveries on synaptic transmission and its impact on network activities. Both experimental and computational works are welcomed, unraveling new properties of specific synapses or how they affect neural networks activity, both in physiological and pathological conditions.

Dr. Simona Tritto
Dr. Lisa Mapelli
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • neurotransmission
  • synapses
  • synaptic plasticity
  • simulation
  • brain
  • brain pathologies
  • neurocomputation

Related Special Issue

Published Papers (7 papers)

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Editorial

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5 pages, 182 KiB  
Editorial
Editorial for This Special Issue “Synaptic Transmission: From Molecular to Neural Network Levels”
by Lisa Mapelli and Simona Tritto
Biomedicines 2024, 12(1), 145; https://doi.org/10.3390/biomedicines12010145 - 10 Jan 2024
Viewed by 590
Abstract
We invited contributions reporting new evidence of synaptic mechanisms and their network-level impacts for this Special Issue [...] Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)

Research

Jump to: Editorial

23 pages, 5763 KiB  
Article
Anisotropy and Frequency Dependence of Signal Propagation in the Cerebellar Circuit Revealed by High-Density Multielectrode Array Recordings
by Anita Monteverdi, Danila Di Domenico, Egidio D’Angelo and Lisa Mapelli
Biomedicines 2023, 11(5), 1475; https://doi.org/10.3390/biomedicines11051475 - 18 May 2023
Cited by 1 | Viewed by 1563
Abstract
The cerebellum is one of the most connected structures of the central nervous system and receives inputs over an extended frequency range. Nevertheless, the frequency dependence of cerebellar cortical processing remains elusive. In this work, we characterized cerebellar cortex responsiveness to mossy fibers [...] Read more.
The cerebellum is one of the most connected structures of the central nervous system and receives inputs over an extended frequency range. Nevertheless, the frequency dependence of cerebellar cortical processing remains elusive. In this work, we characterized cerebellar cortex responsiveness to mossy fibers activation at different frequencies and reconstructed the spread of activity in the sagittal and coronal planes of acute mouse cerebellar slices using a high-throughput high-density multielectrode array (HD-MEA). The enhanced spatiotemporal resolution of HD-MEA revealed the frequency dependence and spatial anisotropy of cerebellar activation. Mossy fiber inputs reached the Purkinje cell layer even at the lowest frequencies, but the efficiency of transmission increased at higher frequencies. These properties, which are likely to descend from the topographic organization of local inhibition, intrinsic electroresponsiveness, and short-term synaptic plasticity, are critical elements that have to be taken into consideration to define the computational properties of the cerebellar cortex and its pathological alterations. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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17 pages, 6455 KiB  
Article
Pimozide Increases a Delayed Rectifier K+ Conductance in Chicken Embryo Vestibular Hair Cells
by Roberta Giunta, Giulia Cheli, Paolo Spaiardi, Giancarlo Russo and Sergio Masetto
Biomedicines 2023, 11(2), 488; https://doi.org/10.3390/biomedicines11020488 - 8 Feb 2023
Viewed by 1388
Abstract
Pimozide is a conventional antipsychotic drug largely used in the therapy for schizophrenia and Tourette’s syndrome. Pimozide is assumed to inhibit synaptic transmission at the CNS by acting as a dopaminergic D2 receptor antagonist. Moreover, pimozide has been shown to block voltage-gated [...] Read more.
Pimozide is a conventional antipsychotic drug largely used in the therapy for schizophrenia and Tourette’s syndrome. Pimozide is assumed to inhibit synaptic transmission at the CNS by acting as a dopaminergic D2 receptor antagonist. Moreover, pimozide has been shown to block voltage-gated Ca2+ and K+ channels in different cells. Despite its widespread clinical use, pimozide can cause several adverse effects, including extrapyramidal symptoms and cardiac arrhythmias. Dizziness and loss of balance are among the most common side effects of pimozide. By using the patch-clamp whole-cell technique, we investigated the effect of pimozide [3 μM] on K+ channels expressed by chicken embryo vestibular type-II hair cells. We found that pimozide slightly blocks a transient outward rectifying A-type K+ current but substantially increases a delayed outward rectifying K+ current. The net result was a significant hyperpolarization of type-II hair cells at rest and a strong reduction of their response to depolarizing stimuli. Our findings are consistent with an inhibitory effect of pimozide on the afferent synaptic transmission by type-II hair cells. Moreover, they provide an additional key to understanding the beneficial/collateral pharmacological effects of pimozide. The finding that pimozide can act as a K+ channel opener provides a new perspective for the use of this drug. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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14 pages, 1323 KiB  
Article
A Proteome-Wide Effect of PHF8 Knockdown on Cortical Neurons Shows Downregulation of Parkinson’s Disease-Associated Protein Alpha-Synuclein and Its Interactors
by Nicodemus E. Oey, Lei Zhou, Christine Hui Shan Chan, Antonius M. J. VanDongen and Eng King Tan
Biomedicines 2023, 11(2), 486; https://doi.org/10.3390/biomedicines11020486 - 8 Feb 2023
Viewed by 1894
Abstract
Synaptic dysfunction may underlie the pathophysiology of Parkinson’s disease (PD), a presently incurable condition characterized by motor and cognitive symptoms. Here, we used quantitative proteomics to study the role of PHD Finger Protein 8 (PHF8), a histone demethylating enzyme found to be mutated [...] Read more.
Synaptic dysfunction may underlie the pathophysiology of Parkinson’s disease (PD), a presently incurable condition characterized by motor and cognitive symptoms. Here, we used quantitative proteomics to study the role of PHD Finger Protein 8 (PHF8), a histone demethylating enzyme found to be mutated in X-linked intellectual disability and identified as a genetic marker of PD, in regulating the expression of PD-related synaptic plasticity proteins. Amongst the list of proteins found to be affected by PHF8 knockdown were Parkinson’s-disease-associated SNCA (alpha synuclein) and PD-linked genes DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1). Findings in this study show that depletion of PHF8 in cortical neurons affects the activity-induced expression of proteins involved in synaptic plasticity, synaptic structure, vesicular release and membrane trafficking, spanning the spectrum of pre-synaptic and post-synaptic transmission. Given that the depletion of even a single chromatin-modifying enzyme can affect synaptic protein expression in such a concerted manner, more in-depth studies will be needed to show whether such a mechanism can be exploited as a potential disease-modifying therapeutic drug target in PD. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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22 pages, 2516 KiB  
Article
Long-Term Synaptic Plasticity Tunes the Gain of Information Channels through the Cerebellum Granular Layer
by Jonathan Mapelli, Giulia Maria Boiani, Egidio D’Angelo, Albertino Bigiani and Daniela Gandolfi
Biomedicines 2022, 10(12), 3185; https://doi.org/10.3390/biomedicines10123185 - 8 Dec 2022
Cited by 1 | Viewed by 1238
Abstract
A central hypothesis on brain functioning is that long-term potentiation (LTP) and depression (LTD) regulate the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granule cells have been shown to control the gain of signals transmitted through the [...] Read more.
A central hypothesis on brain functioning is that long-term potentiation (LTP) and depression (LTD) regulate the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granule cells have been shown to control the gain of signals transmitted through the mossy fiber pathway by exploiting synaptic inhibition in the glomeruli. However, the way LTP and LTD control signal transformation at the single-cell level in the space, time and frequency domains remains unclear. Here, the impact of LTP and LTD on incoming activity patterns was analyzed by combining patch-clamp recordings in acute cerebellar slices and mathematical modeling. LTP reduced the delay, increased the gain and broadened the frequency bandwidth of mossy fiber burst transmission, while LTD caused opposite changes. These properties, by exploiting NMDA subthreshold integration, emerged from microscopic changes in spike generation in individual granule cells such that LTP anticipated the emission of spikes and increased their number and precision, while LTD sorted the opposite effects. Thus, akin with the expansion recoding process theoretically attributed to the cerebellum granular layer, LTP and LTD could implement selective filtering lines channeling information toward the molecular and Purkinje cell layers for further processing. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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17 pages, 2198 KiB  
Article
Long-Term Memory Function Impairments following Sucrose Exposure in Juvenile versus Adult Rats
by Héctor Coirini, Mariana Rey, María Claudia Gonzalez Deniselle and María Sol Kruse
Biomedicines 2022, 10(11), 2723; https://doi.org/10.3390/biomedicines10112723 - 27 Oct 2022
Cited by 3 | Viewed by 1526
Abstract
We previously described that excessive consumption of sucrose during youth produces fear memory and anxiety-like behavior in adulthood. Here, we evaluated whether high cognitive function is also affected by studying early sucrose consumption in object recognition memory (NOR). Male Sprague Dawley rats were [...] Read more.
We previously described that excessive consumption of sucrose during youth produces fear memory and anxiety-like behavior in adulthood. Here, we evaluated whether high cognitive function is also affected by studying early sucrose consumption in object recognition memory (NOR). Male Sprague Dawley rats were tested for short-term, long-term, and consolidated NOR after 25 days of unlimited sucrose access in juvenile (PD 25–50) or adult age (PD 75–100). All rats spent equal time exploring the two objects during the sample phase T1. When animals were exposed for 2, 24 h or 7 days later to a copy of the objects presented in T1 and a novel object, the sucrose-exposed juvenile group failed to distinguish between the familiar and the novel objects in contrast with the rest of the groups. Sucrose-exposed animals developed hypertriglyceridemia and glucose intolerance, but juvenile animals showed increased fasting glycemia and sustained the glucose intolerance longer. Moreover, sucrose decreased hippocampal proBDNF expression in juveniles while it was increased in adults, and sucrose also increased RAGE expression in adults. The NOR exploration ratio correlated negatively with basal glycemia and positively with proBDNF. Taken together, these data suggest that sucrose-induced alterations in glucose metabolism may contribute to a long-term decline in proBDNF and impaired recognition memory. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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16 pages, 3091 KiB  
Article
Purkinje Cell Activity Resonation Generates Rhythmic Behaviors at the Preferred Frequency of 8 Hz
by Staf Bauer, Nathalie van Wingerden, Thomas Jacobs, Annabel van der Horst, Peipei Zhai, Jan-Harm L. F. Betting, Christos Strydis, Joshua J. White, Chris I. De Zeeuw and Vincenzo Romano
Biomedicines 2022, 10(8), 1831; https://doi.org/10.3390/biomedicines10081831 - 29 Jul 2022
Cited by 2 | Viewed by 2227
Abstract
Neural activity exhibits oscillations, bursts, and resonance, enhancing responsiveness at preferential frequencies. For example, theta-frequency bursting and resonance in granule cells facilitate synaptic transmission and plasticity mechanisms at the input stage of the cerebellar cortex. However, whether theta-frequency bursting of Purkinje cells is [...] Read more.
Neural activity exhibits oscillations, bursts, and resonance, enhancing responsiveness at preferential frequencies. For example, theta-frequency bursting and resonance in granule cells facilitate synaptic transmission and plasticity mechanisms at the input stage of the cerebellar cortex. However, whether theta-frequency bursting of Purkinje cells is involved in generating rhythmic behavior has remained neglected. We recorded and optogenetically modulated the simple and complex spike activity of Purkinje cells while monitoring whisker movements with a high-speed camera of awake, head-fixed mice. During spontaneous whisking, both simple spike activity and whisker movement exhibit peaks within the theta band. Eliciting either simple or complex spikes at frequencies ranging from 0.5 to 28 Hz, we found that 8 Hz is the preferred frequency around which the largest movement is induced. Interestingly, oscillatory whisker movements at 8 Hz were also generated when simple spike bursting was induced at 2 and 4 Hz, but never via climbing fiber stimulation. These results indicate that 8 Hz is the resonant frequency at which the cerebellar-whisker circuitry produces rhythmic whisking. Full article
(This article belongs to the Special Issue Synaptic Transmission: From Molecular to Neural Network Levels)
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