Editorial: Insights in synaptic neuroscience 2022

We are delighted to present the inaugural "Insights in Synaptic Neuroscience" article collection. With this Research Topic, our goal was to shed light on the progress made in the past decade in the neuroscience field and on its future challenges to provide a thorough overview of the status of the art of the synaptic neuroscience field. We thus wished to showcase high-impact and authoritative articles on topical research at the frontiers of synaptic neuroscience, to highlight the diversity of research performed in the field of synaptic neuroscience. We originally aimed chiefly for review articles, but we are happy to report that the majority of works in this Research Topic ended up being original research. Below follows a brief editorial discourse of the papers in our collection of articles. Chokshi et al. (2021) explored how the history of neural activity influences synaptic plasticity in the brain. Previous research showed that exposure to darkness followed by light re-exposure leads to a rapid weakening of excitatory synapses onto layer 2/3 pyramidal neurons in the primary visual cortex. The authors tested whether the period in the dark changed cortical plasticity such that the activity elicited by the re-exposure to light depressed the layer 2/3 synapses. To that end they first recorded in vivo in primary visual cortex the spike patterns evoked by re-exposure to light and subsequently they replayed theses spike patterns ex-vivo in slices from dark-exposed and in normal reared control mice. This stimulation, and also a Poisson pattern with the average rate both reduce the synaptic strength in the slices from darkexposed missed, but not in the slices from control mice. These findings suggest that the history of visual experience alters how neurons in primary visual cortex respond to stimulation and that rapid synaptic depression can occur through various neural activity patterns.Synaptic formation and establishment of long-term plasticity are orchestrated by protein complexes, and recent genomic and proteomic studies have uncovered new molecules possibly involved in these processes. In this issue, León et al. (2021) provide an overview of the structure and molecular mechanisms by which glycoprotein M6a participates in synapse formation and maintenance. They summarize evidence collected from patients carrying mutations in the GPM6A gene, animal models, and in vitro studies that together suggest important role for M6a in normal function of synapses and in neurological conditions.Tyro3 is a receptor tyrosine kinase that is expressed in neurons across several key brain areas such as striatum, neocortex, hypothalamus, and hippocampus. Despite this widespread expression, the role of Tyro3 has been unknown. Combining a battery of approaches -e.g., electron microscopy, patch-clamp electrophysiology, cell culturing, acute slices, and Tyro3 In neurotransmitter release, four modes of synaptic vesicle cycling have been identified, yet it has remained unclear which are most biologically relevant. To address this, Paksoy et al. (2022) explored the role of clathrin in synaptic vesicle recycling at the calyx of Held under physiological conditions. They relied on the clathrin inhibitor Pitstop-2 combined with serial sectioning scanning electron microscopy to reveal that, under biologically plausible conditions, clathrin plays a role in synaptic vesicle recycling from both large endosomes as well as the plasma membrane.The balance between glutamatergic excitatory and GABAergic inhibitory synaptic transmission is crucial for information processing in the neocortex. Moreover, even transient disruptions in this balance during early development can contribute to neuropsychiatric disorders later in life. Notably, in the KI mouse line mice the haplodeficiency of the GABA synthetizing enzyme GAD67 does not result in epileptic activity and only in mild behavioral deficits. The examination by Ueberbach et al. (2023) confirmed the expected decrease in fast inhibitory synaptic activity in in this mouse line, yet network activity was seemingly balanced by a compensatory increased tonic activation of the slow GABAB receptors. In turn, the enhanced GABAB receptors were likely to result from increased GABA release via GABA transporter 3 (GAT-3) working in reverse mode.The frontal eye field in primates contains diverse neurons with different functions.While some neurons signal movement and fixation, others also respond to visual stimuli.However, identifying distinct cell types has been challenging. In this volume, Piette et al. (2021) examined biophysical properties of deep layer pyramidal neurons in slices and identified two main subtypes: one with low resistance and low excitability, and another with high resistance and strong excitability. These findings suggest the presence of at least two distinct populations of deep-layer neurons in the frontal eye field, which has implications for understanding visual attention and saccade production.The precuneus -which is part of the human posteromedial cortex -contributes to processing of multimodal information including emotion, social behaviour, and spatial cognition. In an anatomical study of human brain tissue that relied on Nissl and Golgi stains, Fuentealba-Villarroel et al. (2022) reveal that the presence of elongated spindle-shaped neurons in cortical layer 5 that are suggestive of von Economo neurons. These neurons are of interest, because they can be found in humans and other primates, but not in all mammals. A tentative link between these neurons and neuropsychiatric disorders involving the precuneus highlights the need for a better and more detailed understanding of this intriguing cell type.To summarize, this article collection has highlighted recent advances in synaptic neuroscience. We hope and expect that this Research Topic will inspire, inform, and provide direction and guidance to researchers in the emerging subfield of synaptic neuroscience. We would like to extend our gratitude to all the authors who contributed.Author contributions KPL, AK, and PJS wrote the manuscript.

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