567 results
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Journal Article
Visualizing presynaptic calcium dynamics and vesicle fusion with a single genetically encoded reporter at individual synapses
Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis…
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Journal Article
The Shank3 interaction partner ProSAPiP1 regulates postsynaptic SPAR levels and the maturation of dendritic spines in hippocampal neurons
The postsynaptic density or PSD is a submembranous compartment containing a wide array of proteins that contribute to both morphology and function of excitatory glutamatergic synapses. In this study, we have analyzed functional aspects of the Fezzin ProSAPiP1, an interaction partner of the…
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Journal Article
How invariant feature selectivity is achieved in cortex
Making sense of the environment is paramount to survival. Yet, how this accomplished by the nervous system remains largely unknown, even in the comparatively well understood visual system. It is especially unclear how detailed peripheral signal representations are transformed into the…
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Journal Article
Afferent input selects NMDA receptor subtype to determine the persistency of hippocampal LTP in freely behaving mice
The glutamatergic N-methyl-D-aspartate receptor (NMDAR) is critically involved in many forms of hippocampus-dependent memory that may be enabled by synaptic plasticity. Behavioral studies with NMDAR antagonists and NMDAR subunit (GluN2) mutants revealed distinct contributions from GluN2A- and…
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Journal Article
Modulation, plasticity and pathophysiology of the parallel fiber-Purkinje cell synapse
The parallel fiber-Purkinje cell synapse represents the point of maximal signal divergence in the cerebellar cortex with an estimated number of about 60 billion synaptic contacts in the rat and 100,000 billions in humans. At the same time, the Purkinje cell dendritic tree is a site of remarkable…
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Journal Article
Role of Bassoon and Piccolo in assembly and molecular organization of the active zone
Bassoon and Piccolo are two very large scaffolding proteins of the cytomatrix assembled at the active zone (CAZ) where neurotransmitter is released. They share regions of high sequence similarity distributed along their entire length and seem to share both overlapping and distinct functions in…
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Journal Article
Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age
Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent…
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Journal Article
The roles of microtubule-based transport at presynaptic nerve terminals
Targeted intracellular movement of presynaptic proteins plays important roles during synapse formation and, later, in the homeostatic maintenance of mature synapses. Movement of these proteins is mediated by motor complexes travelling along intracellular cytoskeletal networks often in the form of…
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Journal Article
Flash-and-freeze: coordinating optogenetic stimulation with rapid freezing to visualize membrane dynamics at synapses with millisecond resolution
Electron microscopy depicts subcellular structures at synapses exquisitely but only captures static images. To visualize membrane dynamics, we have developed a novel technique, called flash-and-freeze, which induces neuronal activity with a flash of light and captures the membrane dynamics by rapid…
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Journal Article
Organelle-specific sensors for monitoring Ca2+ dynamics in neurons
Calcium (Ca2+) plays innumerable critical functions in neurons ranging from regulation of neurotransmitter release and synaptic plasticity to activity-dependent transcription. Therefore, more than any other cell types, neurons are critically dependent on spatially and temporally controlled Ca2+…
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Journal Article
Norepinephrine release from Locus Ceruleus:a central regulator for the CNS spatio-temporal activation pattern?
Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the…
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Journal Article
Correlative Light Electron Microscopy: Connecting Synaptic Structure and Function
Many core paradigms of contemporary neuroscience are based on information obtained by electron or light microscopy. Intriguingly, these two imaging techniques are often viewed as complementary, yet separate entities. Recent technological advancements in microscopy techniques, labeling tools and…
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Journal Article
MOLECULAR MACHINES DETERMINING THE FATE OF ENDOCYTOSED SYNAPTIC VESICLES IN NERVE TERMINALS
The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions.The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of…
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Journal Article
Optogenetic monitoring of synaptic activity with genetically encoded voltage indicators
The age of genetically encoded voltage indicators has matured to the point that changes in membrane potential can now be observed optically in vivo. Improving the signal size and speed of these voltage sensors has been the primary driving forces during this maturation process. As a result, there is…
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Journal Article
The postsynaptic density: there is more than meets the eye
The postsynaptic density (PSD), apparent in electron micrographs as a dense lamina just beneath the postsynaptic membrane, includes a deeper layer, the pallium, containing a scaffold of Shank and Homer proteins. Though poorly defined in traditionally prepared thin-section electron micrographs, the…
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Journal Article
Can the lateral habenula crack the serotonin code?
The lateral habenula (LHb) and the serotoninergic system both contribute to motivational states by encoding rewarding and aversive signals. Converging evidence suggests that perturbation of these systems is critical for the pathophysiology of mood disorders. Anatomical and functional studies…
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Journal Article
Dopamine D1/D5, but not D2/D3, receptor dependency of synaptic plasticity at hippocampal mossy fiber synapses that is enabled by patterned afferent stimulation, or spatial learning
Although the mossy fiber (MF) synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24h) synaptic plasticity that is akin to that observed at the Schaffer collateral…
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Journal Article
Intrinsic cholinergic neurons in the hippocampus: fact or artefact?
It is generally agreed that hippocampal acetylcholine (ACh) is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history…
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Journal Article
Co-existence of functionally different vesicular neurotransmitter transporters
The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine into synaptic vesicle (SV)…
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Journal Article
The role of multiple neuromodulators in reinforcement learning that is based on competition between eligibility traces
The ability to maximize reward and avoid punishment is essential for animal survival. Reinforcement learning (RL) refers to the algorithms used by biological or artificial systems to learn how to maximize reward or avoid negative outcomes based on past experiences. While RL is also important in…