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Artikel Jurnal
What the Spectrum of Microglial Functions Can Teach us About Fetal Alcohol Spectrum Disorder
Alcohol exposure during gestation can lead to severe defects in brain development and lifelong physical, behavioral and learning deficits that are classified under the umbrella term fetal alcohol spectrum disorder (FASD). Sadly, FASD is diagnosed at an alarmingly high rate, affecting 2%–5% of live…
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Artikel Jurnal
Piccolo Promotes Vesicle Replenishment at a Fast Central Auditory Synapse
Piccolo and Bassoon are the two largest cytomatrix of the active zone (CAZ) proteins involved in scaffolding and regulating neurotransmitter release at presynaptic active zones (AZs), but have long been discussed as being functionally redundant. We employed genetic manipulation to bring forth and…
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Artikel Jurnal
Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits
Many diverse factors, ranging from stress to infections, can perturb brain homeostasis and alter the physiological activity of microglia, the immune cells of the central nervous system. Microglia play critical roles in the process of synaptic maturation and brain wiring during development. Any…
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Artikel Jurnal
Filopodia: A Rapid Structural Plasticity Substrate for Fast Learning
Formation of new synapses between neurons is an essential mechanism for learning and encoding memories. The vast majority of excitatory synapses occur on dendritic spines, therefore, the growth dynamics of spines is strongly related to the plasticity timescales. Especially in the early stages of…
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Artikel Jurnal
Selective Inactivation of Fibroblast Growth Factor 22 (FGF22) in CA3 Pyramidal Neurons Impairs Local Synaptogenesis and Affective Behavior Without Affecting Dentate Neurogenesis
Various growth factors regulate synapse development and neurogenesis, and are essential for brain function. Changes in growth factor signaling are implicated in many neuropsychiatric disorders such as depression, autism and epilepsy. We have previously identified that fibroblast growth factor 22…
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Artikel Jurnal
The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?
Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles…
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Artikel Jurnal
The Active and Periactive Zone Organization and the Functional Properties of Small and Large Synapses
The arrival of an action potential (AP) at a synaptic terminal elicits highly synchronized quanta release. Repetitive APs produce successive synaptic vesicle (SV) fusions that require management of spent synaptic vesicle components in the presynaptic membrane with minimum disturbance of the…
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Artikel Jurnal
Molecular machines regulating the release probability of synaptic vesicles at the active zone.
The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabil-istic process crucial for information transfer. The probability of a SV to release its transmitter content…
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Artikel Jurnal
The iTRAPs: guardians of synaptic vesicle cargo retrieval during endocytosis
The reformation of synaptic vesicles during endocytosis is essential for the maintenance of neurotransmission in central nerve terminals. Newly formed synaptic vesicles must be generated with the correct protein cargo in the correct stoichiometry to be functional for exocytosis. Classical clathrin…
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Artikel Jurnal
Synaptic vesicle proteins and active zone plasticity
Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone. The complex molecular architecture of active zones mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of active zones vary…
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Artikel Jurnal
Inhibition controls asynchronous states of neuronal networks
Computations in cortical circuits require action potentials from excitatory and inhibitory neurons. In this mini-review, I first provide a quick overview of findings that indicate that GABAergic neurons play a fundamental role in coordinating spikes and generating synchronized network activity…
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Artikel Jurnal
Presynaptic molecular determinants of quantal size
The quantal hypothesis for the release of neurotransmitters at the chemical synapse has gained wide acceptance since it was first worked out at the motor endplate in frog skeletal muscle in the 1950s. Considering the morphological identification of synaptic vesicles at the nerve terminals that…
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Artikel Jurnal
The amyloid precursor protein – a novel player within the molecular array of presynaptic nanomachines
More than 20 years ago the amyloid precursor protein (APP) was identified as the precursor protein of the Aβ peptide, the main component of senile plaques in brains affected by Alzheimer´s disease. The pathophysiology of AD, characterized by a massive loss of synapses, cognitive decline, and…
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Artikel Jurnal
Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit
The feedforward dentate gyrus-CA3 microcircuit in the hippocampus is thought to activate ensembles of CA3 pyramidal cells and interneurons to encode and retrieve episodic memories. The creation of these CA3 ensembles depends on neuromodulatory input and synaptic plasticity within this microcircuit…
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Artikel Jurnal
The emergence of NMDA receptor metabotropic function: insights from imaging
The NMDA receptor (R) participates in many important physiological and pathological processes. For example, its activation is required for both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. Furthermore, it may play a…
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Artikel Jurnal
SNAP-25, a known presynaptic protein with emerging postsynaptic functions.
A hallmark of synaptic specializations is their dependence on highly organized complexes of proteins that interact with each other. The loss or modification of key synaptic proteins directly affects the properties of such networks, ultimately impacting synaptic function. SNAP-25 is a component of…
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Artikel Jurnal
Sumoylation in synaptic function and dysfunction
Sumoylation has recently emerged as a key post-translational modification involved in many, if not all, biological processes. Small Ubiquitin-like MOdifiers (SUMOs) polypeptides are covalently attached to specific lysine residues of target proteins through a dedicated enzymatic pathway. Disruption…
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Artikel Jurnal
Control of transmembrane protein diffusion within the postsynaptic density assessed by simultaneous single-molecule tracking and localization microscopy
Postsynaptic transmembrane proteins are critical elements of synapses, mediating trans-cellular contact, sensitivity to neurotransmitters and other signaling molecules, and flux of Ca and other ions. Positioning and mobility of each member of this large class of proteins is critical to their…
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Artikel Jurnal
Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) modulates many key brain functions including those subserving sensation, emotion, reward and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel…