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Artikel Jurnal
The Actin/Spectrin Membrane-Associated Periodic Skeleton in Neurons
Neurons are the most asymmetric cell types, with their axons commonly extending over lengths that are thousand times longer than the diameter of the cell soma. Fluorescence nanoscopy has recently unveiled that actin, spectrin and accompanying proteins form a membrane-associated periodic skeleton…
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Artikel Jurnal
Structure-Activity Investigation of a G Protein-Biased Agonist Reveals Molecular Determinants for Biased Signaling of the D2 Dopamine Receptor
The dopamine D2 receptor (D2R) is known to elicit effects through activating two major signaling pathways mediated by either G proteins (Gi/o) or β-arrestins. However, the specific role of each pathway in physiological or therapeutic activities is not known with certainty. One approach to the…
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Artikel Jurnal
Extrasynaptic Neurotransmission Mediated by Exocytosis and Diffusive Release of Transmitter Substances
This review article deals with the mechanisms of extrasynaptic release of transmitter substances, namely the release from the soma, axon and dendrites in the absence of postsynaptic counterparts. Extrasynaptic release occurs by exocytosis or diffusion. Spillover from the synaptic cleft also…
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Artikel Jurnal
Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells
In fast-spiking (FS), parvalbumin-expressing interneurons of the CA1 hippocampus, activation of the GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) in basal dendrites is coupled to Ca2+-induced Ca2+-release (CICR), and can result in a supralinear summation of postsynaptic Ca2+-transients…
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Artikel Jurnal
Social Stimulus Causes Aberrant Activation of the Medial Prefrontal Cortex in a Mouse Model With Autism-Like Behaviors
Autism spectrum disorder (ASD) is a highly prevalent and genetically heterogeneous brain disorder. Developing effective therapeutic interventions requires knowledge of the brain regions that malfunction and how they malfunction during ASD-relevant behaviors. Our study provides insights into brain…
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Artikel Jurnal
Deficient Wnt Signaling and Synaptic Vulnerability in Alzheimer’s Disease: Emerging Roles for the LRP6 Receptor
Synapse dysfunction and loss represent critical early events in the pathophysiology of Alzheimer’s disease (AD). While extensive research has elucidated the direct synaptotoxic effects of Amyloid-β (Aβ) oligomers, less is known about how signaling pathways at the synapse are affected by Aβ. A…
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Artikel Jurnal
Uncoupling DISC1 × D2R Protein-Protein Interactions Facilitates Latent Inhibition in Disc1-L100P Animal Model of Schizophrenia and Enhances Synaptic Plasticity via D2 Receptors
Both Disrupted-In-Schizophrenia-1 (DISC1) and dopamine receptors D2R have significant contributions to the pathogenesis of schizophrenia. Our previous study demonstrated that DISC1 binds to D2R and such protein-protein interaction is enhanced in patients with schizophrenia and Disc1-L100P mouse…
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Artikel Jurnal
Differential pH Dynamics in Synaptic Vesicles From Intact Glutamatergic and GABAergic Synapses
Synaptic transmission requires the presynaptic release of neurotransmitter from synaptic vesicles (SVs) onto the postsynaptic neuron. Vesicular neurotransmitter transporter proteins, which use a V-ATPase-generated proton gradient, play a crucial role in packaging neurotransmitter into SVs. Recent…
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Artikel Jurnal
Prospects of Zinc Supplementation in Autism Spectrum Disorders and Shankopathies Such as Phelan McDermid Syndrome
The loss of one copy of SHANK3 (SH3 and multiple ankyrin repeat domains 3) in humans highly contributes to Phelan McDermid syndrome (PMDS). In addition, SHANK3 was identified as a major autism candidate gene. Interestingly, the protein encoded by the SHANK3 gene is regulated by zinc. While zinc…
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Artikel Jurnal
Long-Term Effects of Early Life Seizures on Endogenous Local Network Activity of the Mouse Neocortex
Understanding the long term impact of early life seizures (ELS) is of vital importance both for researchers and clinicians. Most experimental studies of how seizures affect the developing brain have drawn their conclusions based on changes detected at the cellular or behavioral level, rather than…
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Artikel Jurnal
Heterogeneous Signaling at GABA and Glycine Co-releasing Terminals
The corelease of several neurotransmitters from a single synaptic vesicle has been observed at many central synapses. Nevertheless, the signaling synergy offered by cotransmission and the mechanisms that maintain the optimal release and detection of neurotransmitters at mixed synapses remain poorly…
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Artikel Jurnal
A Focus on Reward Prediction and the Lateral Habenula: Functional Alterations and the Behavioral Outcomes Induced by Drugs of Abuse
The lateral habenula (LHb) regulates reward learning and controls the updating of reward-related information. Drugs of abuse have the capacity to hijack the cellular and neurocircuit mechanisms mediating reward learning, forming non-adaptable, compulsive behaviors geared toward obtaining illicit…
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Artikel Jurnal
Oxytocin as a Modulator of Synaptic Plasticity: Implications for Neurodevelopmental Disorders
The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat…
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Artikel Jurnal
The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release
Calcium diffusion in the thin 100 nm layer located between the plasma membrane and docked vesicles in the pre-synaptic terminal of neuronal cells mediates vesicular fusion and synaptic transmission. Accounting for the narrow-cusp geometry located underneath the vesicle is a key ingredient that…
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Artikel Jurnal
Molecular Dissection of Neurobeachin Function at Excitatory Synapses
Spines are small protrusions from dendrites where most excitatory synapses reside. Changes in number, shape, and size of dendritic spines often reflect changes of neural activity in entire circuits or at individual synapses, making spines key structures of synaptic plasticity. Neurobeachin is a…
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Artikel Jurnal
Activity-Dependent Phosphorylation by CaMKIIδ Alters the Ca2+ Affinity of the Multi-C2-Domain Protein Otoferlin
Otoferlin is essential for fast Ca2+-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic…
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Artikel Jurnal
Dynamic Arc SUMOylation and Selective Interaction with F-Actin-Binding Protein Drebrin A in LTP Consolidation In Vivo
Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. Post-translation modification by small ubiquitin-like modifier…
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Artikel Jurnal
Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner
Microglia are the resident immune cells of the brain, important for normal neural development in addition to host defense in response to inflammatory stimuli. Air pollution is one of the most pervasive and harmful environmental toxicants in the modern world, and several large scale epidemiological…
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Artikel Jurnal
Function of the Deubiquitinating Enzyme USP46 in the Nervous System and Its Regulation by WD40-Repeat Proteins
Posttranslational modification of proteins by ubiquitin regulates synapse development and synaptic transmission. Much progress has been made investigating the role of ubiquitin ligases at the synapse, however very little is known about the deubiquitinating enzymes (DUBs) which remove ubiquitin from…