2,060 results match your criteria postsynaptic structures

A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation.

Brain Stimul 2021 May 12. Epub 2021 May 12.

Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, Canada.

Background: Deep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications.

Objective: Provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity. Read More

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Ultrastructural analysis of dendritic spine necks reveals a continuum of spine morphologies.

Dev Neurobiol 2021 May 12. Epub 2021 May 12.

Neurotechnology Center, Dept. Biological Sciences, Columbia University, New York, NY, 10027, USA.

Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Read More

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Perineuronal net abnormalities in Slc13a4 mice are rescued by postnatal administration of N-acetylcysteine.

Exp Neurol 2021 May 1:113734. Epub 2021 May 1.

The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Disruptions to either sulfate supply or sulfation enzymes can affect brain development and have long-lasting effects on brain function, yet our understanding of the molecular mechanisms governing this are incomplete. Perineuronal nets (PNNs) are highly sulfated, specialized extracellular matrix structures that regulate the maturation of synaptic connections and neuronal plasticity. We have previously shown that mice heterozygous for the brain sulfate transporter Slc13a4 have abnormal social interactions, memory, exploratory behaviors, stress and anxiety of postnatal origin, pointing to potential deficits in PNN biology, and implicate SLC13A4 as a critical factor required for regulating normal synaptic connectivity and function. Read More

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CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation.

Nat Neurosci 2021 Apr 29. Epub 2021 Apr 29.

Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Read More

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Electrical synaptic transmission requires a postsynaptic scaffolding protein.

Elife 2021 04 28;10. Epub 2021 Apr 28.

Institute of Neuroscience, University of Oregon, Eugene, United States.

Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support. Here, we investigated the functional relationship between neuronal Connexins and Zonula Occludens 1 (ZO1), an intracellular scaffolding protein localized to electrical synapses. Read More

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Nanoscale 3D EM reconstructions reveal intrinsic mechanisms of structural diversity of chemical synapses.

Cell Rep 2021 Apr;35(1):108953

Department of Neuroscience, The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

Chemical synapses of shared cellular origins have remarkably heterogeneous structures, but how this diversity is generated is unclear. Here, we use three-dimensional (3D) electron microscopy and artificial intelligence algorithms for image processing to reconstruct functional excitatory microcircuits in the mouse hippocampus and microcircuits in which neurotransmitter signaling is permanently suppressed with genetic tools throughout the lifespan. These nanoscale analyses reveal that experience is dispensable for morphogenesis of synapses with different geometric shapes and contents of membrane organelles and that arrangement of morphologically distinct connections in local networks is stochastic. Read More

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The NMDA Receptor Subunit (GluN1 and GluN2A) Modulation Following Different Conditions of Cocaine Abstinence in Rat Brain Structures.

Neurotox Res 2021 Jun 24;39(3):556-565. Epub 2021 Mar 24.

Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Smętna 12, 31-343, Kraków, PL, Poland.

Different neuronal alterations within glutamatergic system seem to be crucial for developing of cocaine-seeking behavior. Cocaine exposure provokes a modulation of the NMDA receptor subunit expression in rodents, which probably contributes to cocaine-induced behavioral alterations. The aim of this study was to examine the composition of the NMDA receptor subunits in the brain structures in rats with the history of cocaine self-administration after cocaine abstinence (i) in an enriched environment, (ii) in an isolated condition, (iii) with extinction training, or (iv) without instrumental task, as well as the Grin1 (encoding GluN1) and Grin2A (encoding GluN2A) gene expression were evaluated after 10-day extinction training in rat brain structures. Read More

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Regulation of synaptic nanodomain by liquid-liquid phase separation: A novel mechanism of synaptic plasticity.

Curr Opin Neurobiol 2021 Mar 19;69:84-92. Epub 2021 Mar 19.

Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan. Electronic address:

Advances in microscopy techniques have revealed the details of synaptic nanodomains as defined by the segregation of specific molecules on or beneath both presynaptic and postsynaptic membranes. However, it is yet to be clarified how such segregation is accomplished without demarcating membrane and how nanodomains respond to the neuronal activity. It was recently discovered that proteins at the synapse undergo liquid-liquid phase separation (LLPS), which not only contributes to the accumulation of synaptic proteins but also to further segregating the proteins into subdomains by forming phase-in-phase structures. Read More

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Immunostaining of Whole-Mount Retinas with the CLARITY Tissue Clearing Method.

J Vis Exp 2021 03 6(169). Epub 2021 Mar 6.

Eye Research Institute, Oakland University;

The tissue hydrogel delipidation method (CLARITY), originally developed by the Deisseroth laboratory, has been modified and widely used for immunostaining and imaging of thick brain samples. However, this advanced technology has not yet been used for whole-mount retinas. Although the retina is partially transparent, its thickness of approximately 200 µm (in mice) still limits the penetration of antibodies into the deep tissue as well as reducing light penetration for high-resolution imaging. Read More

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Structural properties and peptide ligand binding of the capsid homology domains of human Arc.

Biochem Biophys Rep 2021 Jul 5;26:100975. Epub 2021 Mar 5.

Department of Biomedicine, University of Bergen, Norway.

The activity-regulated cytoskeleton-associated protein (Arc) is important for synaptic plasticity and the normal function of the brain. Arc interacts with neuronal postsynaptic proteins, but the mechanistic details of its function have not been fully established. The C-terminal domain of Arc consists of tandem domains, termed the N- and C-lobe. Read More

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Therapeutic efficacy of 3,4-Diaminopyridine phosphate on neuromuscular junction in Pompe disease.

Biomed Pharmacother 2021 May 19;137:111357. Epub 2021 Feb 19.

Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan 20133, Italy.

3,4-Diaminopyridine (3,4-DAP) and its phosphate form, 3,4-DAPP have been used efficiently in the past years to treat muscular weakness in myasthenic syndromes with neuromuscular junctions (NMJs) impairment. Pompe disease (PD), an autosomal recessive metabolic disorder due to a defect of the lysosomal enzyme α-glucosidase (GAA), presents some secondary symptoms that are related to neuromuscular transmission dysfunction, resulting in endurance and strength failure. In order to evaluate whether 3,4-DAPP could have a beneficial effect on this pathology, we took advantage of a transient zebrafish PD model that we previously generated and characterized. Read More

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Chronic and Acute Manipulation of Cortical Glutamate Transmission Induces Structural and Synaptic Changes in Co-cultured Striatal Neurons.

Front Cell Neurosci 2021 18;15:569031. Epub 2021 Feb 18.

Centre for Applied Neurogenetics (CAN), University of British Columbia, Vancouver, BC, Canada.

In contrast to the prenatal topographic development of sensory cortices, striatal circuit organization is slow and requires the functional maturation of cortical and thalamic excitatory inputs throughout the first postnatal month. While mechanisms regulating synapse development and plasticity are quite well described at excitatory synapses of glutamatergic neurons in the neocortex, comparatively little is known of how this translates to glutamate synapses onto GABAergic neurons in the striatum. Here we investigate excitatory striatal synapse plasticity in an system, where glutamate can be studied in isolation from dopamine and other neuromodulators. Read More

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February 2021

Trans-synaptic assemblies link synaptic vesicles and neuroreceptors.

Sci Adv 2021 Mar 5;7(10). Epub 2021 Mar 5.

Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo-electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2- to 4-nm scale. Using template-free detection and classification, we showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Read More

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Participation of Glutamatergic Ionotropic Receptors in Excitotoxicity: The Neuroprotective Role of Prolactin.

Neuroscience 2021 05 27;461:180-193. Epub 2021 Feb 27.

Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, CDMX, México 04510, Mexico. Electronic address:

Glutamate (Glu) is known as the main excitatory neurotransmitter in the central nervous system. It can trigger a series of processes ranging from synaptic plasticity to neurophysiological regulation. To carry out its functions, Glu acts via interaction with its cognate receptors, which are ligand-dependent. Read More

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Changes in Presynaptic Gene Expression during Homeostatic Compensation at a Central Synapse.

J Neurosci 2021 Apr 19;41(14):3054-3067. Epub 2021 Feb 19.

Centre for Neural Circuits and Behaviour, University of Oxford, Oxford OX1 3SR, United Kingdom

Homeostatic matching of pre- and postsynaptic function has been observed in many species and neural structures, but whether transcriptional changes contribute to this form of trans-synaptic coordination remains unknown. To identify genes whose expression is altered in presynaptic neurons as a result of perturbing postsynaptic excitability, we applied a transcriptomics-friendly, temperature-inducible Kir2.1-based activity clamp at the first synaptic relay of the olfactory system, a central synapse known to exhibit trans-synaptic homeostatic matching. Read More

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Deletion of LRP1 From Astrocytes Modifies Neuronal Network Activity in an Model of the Tripartite Synapse.

Front Cell Neurosci 2020 14;14:567253. Epub 2021 Jan 14.

Department of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Bochum, Germany.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane receptor that binds over 40 potential ligands and is involved in processes such as cell differentiation, proliferation, and survival. LRP1 is ubiquitously expressed in the organism and enriched among others in blood vessels, liver, and the central nervous system (CNS). There, it is strongly expressed by neurons, microglia, immature oligodendrocytes, and astrocytes. Read More

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January 2021

Helical Fasciculation of Bipolar and Horizontal Cell Neurites for Wiring With Photoreceptors in Macaque and Mouse Retinas.

Invest Ophthalmol Vis Sci 2021 Jan;62(1):31

Studio EM-Retina, Satonaka, Nishinomiya, Hyogo, Japan.

Purpose: The three-dimensional configurations of rod and cone bipolar cell (BC) dendrites and horizontal cell (HC) processes outside rod and cone synaptic terminals have not been fully elucidated. We reveal how these neurites are mutually arranged to coordinate formation and maintenance of the postsynaptic complex of ribbon synapses in mouse and monkey retinas.

Methods: Serial section transmission electron microscopy was utilized to reconstruct BC and HC neurites in macaque monkey and mouse, including metabotropic glutamate receptor 6 (mGluR6)-knockout mice. Read More

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January 2021

Cocaine abstinence modulates NMDA receptor subunit expression: An analysis of the GluN2B subunit in cocaine-seeking behavior.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jan 22;109:110248. Epub 2021 Jan 22.

Maj Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, Poland.

Cocaine use disorder develops in part due to the strong associations formed between drugs and the stimuli associated with drug use. Recently, treatment strategies including manipulations of drug-associated memories have been investigated, and the possibility of interfering with N-methyl-d-aspartate (NMDA)-mediated neurotransmission may represent an important option. The aim of this study was to examine the significance of the NMDA receptor subunit GluN2B at the molecular level (the expression of the GluN2B subunit, the Grin2B gene and the association of GluN2B with postsynaptic density protein 95 (PSD95)) in the brain structures of rats with a history of cocaine self-administration after i) cocaine abstinence with extinction training or ii) cocaine abstinence without instrumental tasks, as well as at the pharmacological level (peripheral or intracranial administration of CP 101,606, a GluN2B subunit antagonist during the cocaine- or cue-induced reinstatement). Read More

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January 2021

Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures.

Nat Commun 2021 01 14;12(1):115. Epub 2021 Jan 14.

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

Both high-fidelity and mismatch-tolerant recombination, catalyzed by RAD51 and DMC1 recombinases, respectively, are indispensable for genomic integrity. Here, we use cryo-EM, MD simulation and functional analysis to elucidate the structural basis for the mismatch tolerance of DMC1. Structural analysis of DMC1 presynaptic and postsynaptic complexes suggested that the lineage-specific Loop 1 Gln244 (Met243 in RAD51) may help stabilize DNA backbone, whereas Loop 2 Pro274 and Gly275 (Val273/Asp274 in RAD51) may provide an open "triplet gate" for mismatch tolerance. Read More

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January 2021

Increased Synaptic Strength and mGlu Receptor Plasticity on Mouse Prefrontal Cortex Intratelencephalic Pyramidal Cells Following Intermittent Access to Ethanol.

Alcohol Clin Exp Res 2021 03 9;45(3):518-529. Epub 2021 Feb 9.

Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.

Background: The medial prefrontal cortex (PFC) is crucial for regulating craving and alcohol seeking in alcohol use disorder (AUD) patients and alcohol seeking in animal models. Maladaptive changes in volitional ethanol (EtOH) intake have been associated with PFC function, yet synaptic adaptations within PFC have not been consistently detected in voluntary drinking rodent models. At least 80% of the neurons in PFC are glutamatergic pyramidal cells. Read More

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Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia.

Neurochem Int 2021 03 1;144:104954. Epub 2021 Jan 1.

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan. Electronic address:

Reelin, an extracellular matrix protein, is secreted by Cajal-Retzius cells and plays crucial roles in the development of brain structures and neuronal functions. Reductions in Reelin cause the brain dysfunctions associated with mental disorders, such as schizophrenia. A recent genome-wide copy number variation analysis of Japanese schizophrenia patients identified a novel deletion in RELN encoding Reelin. Read More

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RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.

Front Cell Dev Biol 2020 8;8:598622. Epub 2020 Dec 8.

Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China.

is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in are known to be associated with X-linked intellectual disability (XLID), Parkinson's disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. Read More

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December 2020

Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions.

Front Mol Neurosci 2020 16;13:568426. Epub 2020 Nov 16.

Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS, United States.

The neuromuscular junction (NMJ) is a chemical synapse formed between a presynaptic motor neuron and a postsynaptic muscle cell. NMJs in most vertebrate species share many essential features; however, some differences distinguish human NMJs from others. This review will describe the pre- and postsynaptic structures of human NMJs and compare them to NMJs of laboratory animals. Read More

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November 2020

Development of an N-Cadherin Biofunctionalized Hydrogel to Support the Formation of Synaptically Connected Neural Networks.

ACS Biomater Sci Eng 2020 10 4;6(10):5811-5822. Epub 2020 Sep 4.

Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.

models of the human central nervous system (CNS), particularly those derived from induced pluripotent stem cells (iPSCs), are becoming increasingly recognized as useful complements to animal models for studying neurological diseases and developing therapeutic strategies. However, many current three-dimensional (3D) CNS models suffer from deficits that limit their research utility. In this work, we focused on improving the interactions between the extracellular matrix (ECM) and iPSC-derived neurons to support model development. Read More

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October 2020

Medicinal chemistry, pharmacology, and therapeutic potential of α-conotoxins antagonizing the α9α10 nicotinic acetylcholine receptor.

Pharmacol Ther 2021 Jun 10;222:107792. Epub 2020 Dec 10.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China; Innovation Platform of Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong 266100, China. Electronic address:

α-Conotoxins are disulfide-rich and well-structured peptides, most of which can block nicotinic acetylcholine receptors (nAChRs) with exquisite selectivity and potency. There are various nAChR subtypes, of which the α9α10 nAChR functions as a heteromeric ionotropic receptor in the mammalian cochlea and mediates postsynaptic transmission from the medial olivocochlear. The α9α10 nAChR subtype has also been proposed as a target for the treatment of neuropathic pain and the suppression of breast cancer cell proliferation. Read More

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KLHL17/Actinfilin, a brain-specific gene associated with infantile spasms and autism, regulates dendritic spine enlargement.

J Biomed Sci 2020 Dec 1;27(1):103. Epub 2020 Dec 1.

Institute of Molecular Biology, Academia Sinica, 128, Academia Road, Section 2, Taipei, 11529, Taiwan, Republic of China.

Background: Dendritic spines, the actin-rich protrusions emerging from dendrites, are the subcellular locations of excitatory synapses in the mammalian brain. Many actin-regulating molecules modulate dendritic spine morphology. Since dendritic spines are neuron-specific structures, it is reasonable to speculate that neuron-specific or -predominant factors are involved in dendritic spine formation. Read More

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December 2020

Minimal Number of Required Inputs for Temporally Precise Action Potential Generation in Auditory Brainstem Nuclei.

Front Cell Neurosci 2020 5;14:592213. Epub 2020 Nov 5.

Institute of Zoology, University of Veterinary Medicine, Hannover, Germany.

The auditory system relies on temporal precise information transfer, requiring an interplay of synchronously activated inputs and rapid postsynaptic integration. During late postnatal development synaptic, biophysical, and morphological features change to enable mature auditory neurons to perform their appropriate function. How the number of minimal required input fibers and the relevant EPSC time course integrated for action potential generation changes during late postnatal development is unclear. Read More

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November 2020

Proteomic comparison of different synaptosome preparation procedures.

Amino Acids 2020 Dec 19;52(11-12):1529-1543. Epub 2020 Nov 19.

Laboratory of Proteomics, Institute of Biology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary.

Synaptosomes are frequently used research objects in neurobiology studies focusing on synaptic transmission as they mimic several aspects of the physiological synaptic functions. They contain the whole apparatus for neurotransmission, the presynaptic nerve ending with synaptic vesicles, synaptic mitochondria and often a segment of the postsynaptic membrane along with the postsynaptic density is attached to its outer surface. As being artificial functional organelles, synaptosomes are viable for several hours, retain their activity, membrane potential, and capable to store, release, and reuptake neurotransmitters. Read More

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December 2020

Arrangement of Excitatory Synaptic Inputs on Dendrites of the Medial Superior Olive.

J Neurosci 2021 01 18;41(2):269-283. Epub 2020 Nov 18.

Department Biology II, Ludwig-Maximilians-Universität München, München, Germany, 82152

Neurons in the medial superior olive (MSO) detect 10 µs differences in the arrival times of a sound at the two ears. Such acuity requires exquisitely precise integration of binaural synaptic inputs. There is substantial understanding of how neuronal phase locking of afferent MSO structures, and MSO membrane biophysics subserve such high precision. Read More

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January 2021

Activity-Dependent Remodeling of Synaptic Protein Organization Revealed by High Throughput Analysis of STED Nanoscopy Images.

Front Neural Circuits 2020 15;14:57. Epub 2020 Oct 15.

CERVO Brain Research Centre, Québec, QC, Canada.

The organization of proteins in the apposed nanodomains of pre- and postsynaptic compartments is thought to play a pivotal role in synaptic strength and plasticity. As such, the alignment between pre- and postsynaptic proteins may regulate, for example, the rate of presynaptic release or the strength of postsynaptic signaling. However, the analysis of these structures has mainly been restricted to subsets of synapses, providing a limited view of the diversity of synaptic protein cluster remodeling during synaptic plasticity. Read More

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October 2020