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Neuron Jul 2012Neurotransmitters are released by synaptic vesicle exocytosis at the active zone of a presynaptic nerve terminal. In this review, I discuss the molecular composition and... (Review)
Review
Neurotransmitters are released by synaptic vesicle exocytosis at the active zone of a presynaptic nerve terminal. In this review, I discuss the molecular composition and function of the active zone. Active zones are composed of an evolutionarily conserved protein complex containing as core constituents RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins. This complex docks and primes synaptic vesicles for exocytosis, recruits Ca(2+) channels to the site of exocytosis, and positions the active zone exactly opposite to postsynaptic specializations via transsynaptic cell-adhesion molecules. Moreover, this complex mediates short- and long-term plasticity in response to bursts of action potentials, thus critically contributing to the computational power of a synapse.
Topics: Animals; Exocytosis; Humans; Neuronal Plasticity; Neurotransmitter Agents; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 22794257
DOI: 10.1016/j.neuron.2012.06.012 -
International Journal of Molecular... May 2019Presynaptic Ca entry occurs through voltage-gated Ca (Ca) channels which are activated by membrane depolarization. Depolarization accompanies neuronal firing and... (Review)
Review
Presynaptic Ca entry occurs through voltage-gated Ca (Ca) channels which are activated by membrane depolarization. Depolarization accompanies neuronal firing and elevation of Ca triggers neurotransmitter release from synaptic vesicles. For synchronization of efficient neurotransmitter release, synaptic vesicles are targeted by presynaptic Ca channels forming a large signaling complex in the active zone. The presynaptic Ca2 channel gene family (comprising Ca2.1, Ca2.2, and Ca2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are responsible for channel modulation by interacting with regulatory proteins. This article overviews modulation of the activity of Ca2.1 and Ca2.2 channels in the control of synaptic strength and presynaptic plasticity.
Topics: Animals; Calcium Channels, N-Type; Calcium-Binding Proteins; Humans; Presynaptic Terminals; Synaptic Potentials
PubMed: 31064106
DOI: 10.3390/ijms20092217 -
Neuron Jan 2010Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed... (Comparative Study)
Comparative Study
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.
Topics: Age Factors; Animals; Brain; Brain Chemistry; Learning; Magnesium; Male; Memory; Presynaptic Terminals; Rats; Rats, Sprague-Dawley
PubMed: 20152124
DOI: 10.1016/j.neuron.2009.12.026 -
Current Opinion in Neurobiology Feb 2019Plastic changes in synaptic transmission are thought to underlie learning and memory formation. However, changes in synaptic function are only meaningful in the context... (Review)
Review
Plastic changes in synaptic transmission are thought to underlie learning and memory formation. However, changes in synaptic function are only meaningful in the context of stable baseline function. Accumulating evidence suggests that homeostatic signaling systems actively stabilize synaptic transmission in response to neural activity perturbation. Homeostatic mechanisms control both presynaptic and postsynaptic function. Here, we review recent advances in the field of presynaptic homeostatic plasticity (PHP). We discuss PHP in the context of basic mechanisms controlling neurotransmitter release, highlight emerging similarities between different synapses in different species, and summarize new insights into the molecular mechanisms underlying this evolutionary conserved form of synaptic plasticity.
Topics: Animals; Homeostasis; Neuronal Plasticity; Presynaptic Terminals; Signal Transduction
PubMed: 30384022
DOI: 10.1016/j.conb.2018.10.003 -
Neuron Aug 2022Learning and memory rely on long-lasting, synapse-specific modifications. Although postsynaptic forms of plasticity typically require local protein synthesis, whether...
Learning and memory rely on long-lasting, synapse-specific modifications. Although postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remain unclear. Here, we examined the mouse hippocampal mossy fiber (MF)-CA3 synapse, which expresses both structural and functional presynaptic plasticity and contains presynaptic fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein involved in postsynaptic protein-synthesis-dependent plasticity. We report that MF boutons contain ribosomes and synthesize protein locally. The long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with the translation-dependent enlargement of MF boutons. Remarkably, increasing in vitro or in vivo MF activity enhanced the protein synthesis in MFs. Moreover, the deletion of presynaptic FMRP blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic MF plasticity. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature mammalian brain.
Topics: Animals; Fragile X Mental Retardation Protein; Long-Term Potentiation; Mammals; Mice; Mossy Fibers, Hippocampal; Neuronal Plasticity; Presynaptic Terminals; Ribonucleoproteins; Synapses
PubMed: 35728596
DOI: 10.1016/j.neuron.2022.05.024 -
Journal of Neurochemistry Dec 2016Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in... (Review)
Review
Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in an orderly fashion. In each synapse, a presynaptic terminal loaded with neurotransmitters-containing synaptic vesicles is perfectly aligned to an array of receptors in the postsynaptic membrane. Presynaptic differentiation, which encompasses the events underlying assembly of new presynaptic units, has seen notable advances in recent years. It is now consensual that as a growing axon encounters the receptive dendrites of its partner, presynaptic assembly will be triggered and specified by multiple postsynaptically-derived factors including soluble molecules and cell adhesion complexes. Presynaptic material that reaches these distant sites by axonal transport in the form of pre-assembled packets will be retained and clustered, ultimately giving rise to a presynaptic bouton. This review focuses on the cellular and molecular aspects of presynaptic differentiation in the central nervous system, with a particular emphasis on the identity of the instructive factors and the intracellular processes used by neuronal cells to assemble functional presynaptic terminals. We provide a detailed description of the mechanisms leading to the formation of new presynaptic terminals. In brief, soma-derived packets of pre-assembled material are trafficked to distant axonal sites. Synaptogenic factors from dendritic or glial provenance activate downstream intra-axonal mediators to trigger clustering of passing material and their correct organization into a new presynaptic bouton. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".
Topics: Animals; Axons; Cell Differentiation; Dendrites; Humans; Presynaptic Terminals; Synapses
PubMed: 27315450
DOI: 10.1111/jnc.13702 -
Neuromolecular Medicine Sep 2017Typically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals... (Review)
Review
Typically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals invaginate-entirely or partially-into postsynaptic processes. We survey these invaginating presynaptic terminals in all animals and describe several examples from the central nervous system, including giant fiber systems in invertebrates, and cup-shaped spines, electroreceptor synapses, and some specialized auditory and vestibular nerve terminals in vertebrates. We then examine mechanoreceptors and photoreceptors, concentrating on the complex of pre- and postsynaptic processes found in basal invaginations of the cell. We discuss in detail the role of vertebrate invaginating horizontal cell processes in both chemical and electrical feedback mechanisms. We also discuss the common presence of indenting or invaginating terminals in neuromuscular junctions on muscles of most kinds of animals, and especially discuss those of Drosophila and vertebrates. Finally, we consider broad questions about the advantages of possessing invaginating presynaptic terminals and describe some effects of aging and disease, especially on neuromuscular junctions. We suggest that the invagination is a mechanism that can enhance both chemical and electrical interactions at the synapse.
Topics: Animals; Dendrites; Invertebrates; Mechanoreceptors; Motor Neurons; Neuromuscular Junction; Neurons, Afferent; Photoreceptor Cells; Presynaptic Terminals; Species Specificity; Synapses; Synaptic Transmission; Vertebrates
PubMed: 28612182
DOI: 10.1007/s12017-017-8445-y -
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 -
Biomolecules Jan 2022Synaptic transmission is essential for controlling motor functions and maintaining brain functions such as walking, breathing, cognition, learning, and memory.... (Review)
Review
Synaptic transmission is essential for controlling motor functions and maintaining brain functions such as walking, breathing, cognition, learning, and memory. Neurotransmitter release is regulated by presynaptic molecules assembled in active zones of presynaptic terminals. The size of presynaptic terminals varies, but the size of a single active zone and the types of presynaptic molecules are highly conserved among neuromuscular junctions (NMJs) and central synapses. Three parameters play an important role in the determination of neurotransmitter release properties at NMJs and central excitatory/inhibitory synapses: the number of presynaptic molecular clusters, the protein families of the presynaptic molecules, and the distance between presynaptic molecules and voltage-gated calcium channels. In addition, dysfunction of presynaptic molecules causes clinical symptoms such as motor and cognitive decline in patients with various neurological disorders and during aging. This review focuses on the molecular mechanisms responsible for the functional similarities and differences between excitatory and inhibitory synapses in the peripheral and central nervous systems, and summarizes recent findings regarding presynaptic molecules assembled in the active zone. Furthermore, we discuss the relationship between functional alterations of presynaptic molecules and dysfunction of NMJs or central synapses in diseases and during aging.
Topics: Aging; Humans; Neuromuscular Junction; Presynaptic Terminals; Synapses; Synaptic Transmission
PubMed: 35204679
DOI: 10.3390/biom12020179 -
Function (Oxford, England) 2021Voltage-gated calcium channels are the principal conduits for depolarization-mediated Ca entry into excitable cells. In this review, the biophysical properties of the... (Review)
Review
Voltage-gated calcium channels are the principal conduits for depolarization-mediated Ca entry into excitable cells. In this review, the biophysical properties of the relevant members of this family of channels, those that are present in presynaptic terminals, will be discussed in relation to their function in mediating neurotransmitter release. Voltage-gated calcium channels have properties that ensure they are specialized for particular roles, for example, differences in their activation voltage threshold, their various kinetic properties, and their voltage-dependence of inactivation. All these attributes play into the ability of the various voltage-gated calcium channels to participate in different patterns of presynaptic vesicular release. These include synaptic transmission resulting from single action potentials, and longer-term changes mediated by bursts or trains of action potentials, as well as release resulting from graded changes in membrane potential in specialized sensory synapses.
Topics: Presynaptic Terminals; Calcium Channels; Synaptic Transmission; Synapses; Action Potentials
PubMed: 33313507
DOI: 10.1093/function/zqaa027