-
Current Opinion in Neurobiology Apr 2011In response to calcium influx, synaptic vesicles fuse very rapidly with the plasma membrane to release their neurotransmitter content. An important mechanism for... (Review)
Review
In response to calcium influx, synaptic vesicles fuse very rapidly with the plasma membrane to release their neurotransmitter content. An important mechanism for sustained release includes the formation of new vesicles by local endocytosis. How synaptic vesicles are trafficked from the sites of endocytosis to the sites of release and how they are maintained at the release sites remain poorly understood. Recent studies using fast freezing immobilization and electron tomography have led to insights on the ultrastructural organization of presynaptic boutons and how these structural elements may maintain synaptic vesicles and organize their exocytosis at particular areas of the plasma membrane.
Topics: Animals; Exocytosis; Humans; Presynaptic Terminals; Protein Transport; Synaptic Vesicles
PubMed: 21247753
DOI: 10.1016/j.conb.2010.12.003 -
International Journal of Molecular... Jul 2019Synaptosomes are used to decipher the mechanisms involved in chemical transmission, since they permit highlighting the mechanisms of transmitter release and confirming... (Review)
Review
Synaptosomes are used to decipher the mechanisms involved in chemical transmission, since they permit highlighting the mechanisms of transmitter release and confirming whether the activation of presynaptic receptors/enzymes can modulate this event. In the last two decades, important progress in the field came from the observations that synaptosomes retain changes elicited by both "in vivo" and "in vitro" chemical stimulation. The novelty of these studies is the finding that these adaptations persist beyond the washout of the triggering drug, emerging subsequently as functional modifications of synaptosomal performances, including release efficiency. These findings support the conclusion that synaptosomes are plastic entities that respond dynamically to ambient stimulation, but also that they "learn and memorize" the functional adaptation triggered by exposure to chemical agents. This work aims at reviewing the results so far available concerning this form of synaptosomal learning, also highlighting the role of these chemical adaptations in pathological conditions.
Topics: Adaptation, Physiological; Animals; Disease Susceptibility; Glutamic Acid; Humans; Learning; Memory; Neurotransmitter Agents; Presynaptic Terminals; Receptors, Cell Surface; Synaptosomes
PubMed: 31349638
DOI: 10.3390/ijms20153641 -
ACS Chemical Neuroscience Jan 2015A great deal of research has focused on investigating neurobiological alterations induced by chronic psychostimulant use in an effort to describe, understand, and treat... (Review)
Review
A great deal of research has focused on investigating neurobiological alterations induced by chronic psychostimulant use in an effort to describe, understand, and treat the pathology of psychostimulant addiction. It has been known for several decades that dopamine neurotransmission in the nucleus accumbens is integrally involved in the selection and execution of motivated and goal-directed behaviors, and that psychostimulants act on this system to exert many of their effects. As such, a large body of work has focused on defining the consequences of psychostimulant use on dopamine signaling in the striatum as it relates to addictive behaviors. Here, we review presynaptic dopamine terminal alterations observed following self-administration of cocaine and amphetamine, as well as possible mechanisms by which these alterations occur and their impact on the progression of addiction.
Topics: Adaptation, Biological; Animals; Central Nervous System Stimulants; Dopamine; Humans; Presynaptic Terminals; Self Administration
PubMed: 25491345
DOI: 10.1021/cn5002705 -
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 -
Proceedings of the Japan Academy.... 2015Classically, the basic concept of chemical synaptic transmission was established at the frog neuromuscular junction, and direct intracellular recordings from presynaptic... (Review)
Review
Classically, the basic concept of chemical synaptic transmission was established at the frog neuromuscular junction, and direct intracellular recordings from presynaptic terminals at the squid giant presynaptic terminal have further clarified principles of neurotransmitter release. More recently, whole-cell patch-camp recordings from the calyx of Held in rodent brainstem slices have extended the classical concept to mammalian synapses providing new insights into the mechanisms underlying strength and precision of neurotransmission and developmental changes therein. This review summarizes findings from our laboratory and others on these subjects, mainly at the calyx of Held, with a particular focus on precise, high-fidelity, fast neurotransmission. The mechanisms by which presynaptic terminals acquire strong, precise neurotransmission during postnatal development are also discussed.
Topics: Animals; Central Nervous System; Growth and Development; Humans; Presynaptic Terminals; Probability; Synaptic Transmission
PubMed: 26194855
DOI: 10.2183/pjab.91.305 -
Current Opinion in Neurobiology Jun 2012The unique ability of chemical synapses to transmit information relies on the structural organization of presynaptic terminals. Empowered by forward genetics, research... (Review)
Review
The unique ability of chemical synapses to transmit information relies on the structural organization of presynaptic terminals. Empowered by forward genetics, research using Caenorhabditis elegans has continued to make pivotal contributions to discover conserved regulators and pathways for presynaptic development. Recent advances in microscopy have begun to pave the path for linking molecular dynamics with subsynaptic structures. Studies using diverse reporters for synapses further broaden the landscape of regulatory mechanisms underlying presynaptic differentiation. The identification of novel regulators at transcriptional and post-transcriptional levels raises new questions for understanding synapse formation at the genomic scale.
Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Presynaptic Terminals; Synapses; Ultrasonography
PubMed: 22036768
DOI: 10.1016/j.conb.2011.10.002 -
PloS One 2015Synaptic neurotransmission is known to be an energy demanding process. At the presynapse, ATP is required for loading neurotransmitters into synaptic vesicles, for...
Synaptic neurotransmission is known to be an energy demanding process. At the presynapse, ATP is required for loading neurotransmitters into synaptic vesicles, for priming synaptic vesicles before release, and as a substrate for various kinases and ATPases. Although it is assumed that presynaptic sites usually harbor local mitochondria, which may serve as energy powerhouse to generate ATP as well as a presynaptic calcium depot, a clear role of presynaptic mitochondria in biochemical functioning of the presynapse is not well-defined. Besides a few synaptic subtypes like the mossy fibers and the Calyx of Held, most central presynaptic sites are either en passant or tiny axonal terminals that have little space to accommodate a large mitochondrion. Here, we have used imaging studies to demonstrate that mitochondrial antigens poorly co-localize with the synaptic vesicle clusters and active zone marker in the cerebral cortex, hippocampus and the cerebellum. Confocal imaging analysis on neuronal cultures revealed that most neuronal mitochondria are either somatic or distributed in the proximal part of major dendrites. A large number of synapses in culture are devoid of any mitochondria. Electron micrographs from neuronal cultures further confirm our finding that the majority of presynapses may not harbor resident mitochondria. We corroborated our ultrastructural findings using serial block face scanning electron microscopy (SBFSEM) and found that more than 60% of the presynaptic terminals lacked discernible mitochondria in the wild-type mice hippocampus. Biochemical fractionation of crude synaptosomes into mitochondria and pure synaptosomes also revealed a sparse presence of mitochondrial antigen at the presynaptic boutons. Despite a low abundance of mitochondria, the synaptosomal membranes were found to be highly enriched in ATP suggesting that the presynapse may possess alternative mechanism/s for concentrating ATP for its function. The potential mechanisms including local glycolysis and the possible roles of ATP-binding synaptic proteins such as synapsins, are discussed.
Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Mitochondria; Presynaptic Terminals; Synaptosomes
PubMed: 25928229
DOI: 10.1371/journal.pone.0125185 -
Current Opinion in Neurobiology Aug 2018Regulated release of neurotransmitter depends on the orchestrated function of a large number of proteins in the presynaptic compartment. When synaptic vesicles fuse with... (Review)
Review
Regulated release of neurotransmitter depends on the orchestrated function of a large number of proteins in the presynaptic compartment. When synaptic vesicles fuse with the plasma membrane, these membranes and the attached proteins are endocytosed and either recycled or degraded. This turnover needs to be tightly regulated in a timely and spatially confined manner. Increasing evidence suggests that these mechanisms do not only serve for the removal of defective synaptic vesicles or structural proteins of the active zone but also contribute to pathways regulating synaptic strength. The corresponding presynaptic autophagy system thus appears also important for synaptic maintenance and plasticity. Exciting new studies provide evidence how the autophagy machinery recognizes and degrades synaptic components and lay the ground to understand how autophagy in the presynaptic compartment contributes to modulation and maintenance of synaptic function.
Topics: Animals; Autophagy; Nerve Tissue Proteins; Neuronal Plasticity; Neurotransmitter Agents; Presynaptic Terminals
PubMed: 29549710
DOI: 10.1016/j.conb.2018.02.023 -
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 -
Trends in Neurosciences Feb 1997Nicotinic ACh (nACh) receptors in the CNS are composed of a diverse array of subunits and have a range of pharmacological properties. However, despite the fact that they... (Review)
Review
Nicotinic ACh (nACh) receptors in the CNS are composed of a diverse array of subunits and have a range of pharmacological properties. However, despite the fact that they are ligand-gated cation channels, their physiological functions have not been determined. This has led to increased interest in presynaptic nACh receptors that act to modulate the release of transmitter from presynaptic terminals.
Topics: Animals; Brain; Presynaptic Terminals; Rats; Receptors, Nicotinic
PubMed: 9023878
DOI: 10.1016/s0166-2236(96)10073-4