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Neuroscience Letters Mar 2020Synaptic transmission relies on the fast, synchronous fusion of neurotransmitter filled vesicles with the presynaptic membrane. Synaptotagmin is the Ca sensor that... (Review)
Review
Synaptic transmission relies on the fast, synchronous fusion of neurotransmitter filled vesicles with the presynaptic membrane. Synaptotagmin is the Ca sensor that couples the Ca influx into nerve terminals following an action potential with this fast, synchronous vesicle fusion. Over two decades of synaptotagmin research has provided many clues as to how Ca binding by synaptotagmin may lead to vesicle fusion. In vitro studies of molecular binding interactions are essential for elucidating potential mechanisms. However, an in vivo system to evaluate the postulated mechanisms is required to determine functional significance. The neuromuscular junction (NMJ) has long been an indispensable tool for synaptic research and studies at the NMJ will undoubtedly continue to provide key insights into synaptotagmin function.
Topics: Action Potentials; Animals; Calcium; Humans; Membrane Fusion; Neuromuscular Junction; Static Electricity; Synaptic Transmission; Synaptotagmins
PubMed: 32057923
DOI: 10.1016/j.neulet.2020.134834 -
Neuroscience Feb 2021
Topics: Long-Term Potentiation; Neuronal Plasticity; Synaptic Transmission
PubMed: 33551045
DOI: 10.1016/j.neuroscience.2020.10.006 -
Nature Reviews. Neuroscience Jan 2022Synaptic activity imposes large energy demands that are met by local adenosine triphosphate (ATP) synthesis through glycolysis and mitochondrial oxidative... (Review)
Review
Synaptic activity imposes large energy demands that are met by local adenosine triphosphate (ATP) synthesis through glycolysis and mitochondrial oxidative phosphorylation. ATP drives action potentials, supports synapse assembly and remodelling, and fuels synaptic vesicle filling and recycling, thus sustaining synaptic transmission. Given their polarized morphological features - including long axons and extensive branching in their terminal regions - neurons face exceptional challenges in maintaining presynaptic energy homeostasis, particularly during intensive synaptic activity. Recent studies have started to uncover the mechanisms and signalling pathways involved in activity-dependent and energy-sensitive regulation of presynaptic energetics, or 'synaptoenergetics'. These conceptual advances have established the energetic regulation of synaptic efficacy and plasticity as an exciting research field that is relevant to a range of neurological disorders associated with bioenergetic failure and synaptic dysfunction.
Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Glycolysis; Humans; Receptors, Presynaptic; Synaptic Transmission; Synaptic Vesicles
PubMed: 34782781
DOI: 10.1038/s41583-021-00535-8 -
Annual Review of Neuroscience Jul 2022Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the... (Review)
Review
Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.
Topics: Antidepressive Agents; Depression; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 35508195
DOI: 10.1146/annurev-neuro-110920-040422 -
Nature Neuroscience Aug 2020A group of neurons can generate patterns of activity that represent information about stimuli; subsequently, the group can transform and transmit activity patterns... (Review)
Review
A group of neurons can generate patterns of activity that represent information about stimuli; subsequently, the group can transform and transmit activity patterns across synapses to spatially distributed areas. Recent studies in neuroscience have begun to independently address the two components of information processing: the representation of stimuli in neural activity and the transmission of information in networks that model neural interactions. Yet only recently are studies seeking to link these two types of approaches. Here we briefly review the two separate bodies of literature; we then review the recent strides made to address this gap. We continue with a discussion of how patterns of activity evolve from one representation to another, forming dynamic representations that unfold on the underlying network. Our goal is to offer a holistic framework for understanding and describing neural information representation and transmission while revealing exciting frontiers for future research.
Topics: Animals; Brain; Cognition; Humans; Nerve Net; Neural Networks, Computer; Neurons; Synaptic Transmission
PubMed: 32541963
DOI: 10.1038/s41593-020-0653-3 -
Anatomical Science International Jun 2021Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most... (Review)
Review
Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most excitatory synapses of pyramidal neurons are formed on spines, which are tiny protrusions extending from the dendritic shaft. The spine contains specialized molecular machinery that regulates synaptic transmission and plasticity. Spine size correlates with the efficacy of synaptic transmission, and spine morphology affects signal transduction at the post-synaptic compartment. Plasticity-related changes in the structural and molecular organization of spine synapses are thought to underlie the cellular basis of learning and memory. Recent advances in super-resolution microscopy have revealed the molecular mechanisms of the nanoscale synaptic structures regulating synaptic transmission and plasticity in living neurons, which are difficult to investigate using electron microscopy alone. In this review, we summarize recent advances in super-resolution imaging of spine synapses and discuss the implications of nanoscale structures in the regulation of synaptic function, learning, and memory.
Topics: Animals; Dendritic Spines; Humans; Microscopy; Neuronal Plasticity; Neurons; Prosencephalon; Synapses; Synaptic Transmission
PubMed: 33459976
DOI: 10.1007/s12565-021-00603-0 -
Cell Reports Mar 2023The lateral habenula (LHb) encodes aversive states, and its dysregulation is implicated in neuropsychiatric disorders, including depression. The endocannabinoid (eCB)...
The lateral habenula (LHb) encodes aversive states, and its dysregulation is implicated in neuropsychiatric disorders, including depression. The endocannabinoid (eCB) system is a neuromodulatory signaling system that broadly serves to counteract the adverse effects of stress; however, CB receptor signaling within the LHb can paradoxically promote anxiogenic- and depressive-like effects. Current reports of synaptic actions of eCBs in the LHb are conflicting and lack systematic investigation of eCB regulation of excitatory and inhibitory transmission. Here, we report that eCBs differentially regulate glutamatergic and GABAergic transmission in the LHb, exhibiting canonical and circuit-specific inhibition of both systems and an opposing potentiation of synaptic glutamate release mediated via activation of CB receptors on astrocytes. Moreover, simultaneous depression of GABA and potentiation of glutamate release increases the net excitation-inhibition ratio onto LHb neurons, suggesting a potential cellular mechanism by which cannabinoids may promote LHb activity and subsequent anxious- and depressive-like aversive states.
Topics: Rats; Animals; Endocannabinoids; Habenula; Astrocytes; Rats, Sprague-Dawley; Synaptic Transmission; Glutamates
PubMed: 36842084
DOI: 10.1016/j.celrep.2023.112159 -
Molecular Brain Jan 2024O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes:... (Review)
Review
O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.
Topics: Humans; Protein Processing, Post-Translational; Synaptic Transmission; Proteins; Neurons; Diabetes Mellitus
PubMed: 38167470
DOI: 10.1186/s13041-023-01072-4 -
Alcoholism, Clinical and Experimental... Jan 2020Alcohol addiction causes major health problems throughout the world, causing numerous deaths and incurring a huge economic burden to society. To develop an intervention... (Review)
Review
Alcohol addiction causes major health problems throughout the world, causing numerous deaths and incurring a huge economic burden to society. To develop an intervention for alcohol addiction, it is necessary to identify molecular target(s) of alcohol and associated molecular mechanisms of alcohol action. The functions of many central and peripheral synapses are impacted by low concentrations of ethanol (EtOH). While the postsynaptic targets and mechanisms are studied extensively, there are limited studies on the presynaptic targets and mechanisms. This article is an endeavor in this direction, focusing on the effect of EtOH on the presynaptic proteins associated with the neurotransmitter release machinery. Studies on the effects of EtOH at the levels of gene, protein, and behavior are highlighted in this article.
Topics: Alcoholism; Animals; Ethanol; Humans; Presynaptic Terminals; Protein Structure, Secondary; Protein Structure, Tertiary; SNARE Proteins; Synapses; Synaptic Transmission
PubMed: 31724225
DOI: 10.1111/acer.14238 -
Scientific Reports Oct 2020Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical...
Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy-the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.
Topics: Animals; Chiroptera; Gene Expression; Hippocampus; Learning; Memory; Mice; Neural Pathways; Neuronal Plasticity; Shrews; Species Specificity; Synaptic Transmission; Synaptotagmins
PubMed: 33024184
DOI: 10.1038/s41598-020-73547-6