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Science (New York, N.Y.) Mar 2024The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic... (Review)
Review
The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and "flash-and-freeze" electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.
Topics: Mossy Fibers, Hippocampal; Presynaptic Terminals; Synaptic Transmission; CA3 Region, Hippocampal; Pyramidal Cells; Humans; Animals
PubMed: 38452088
DOI: 10.1126/science.adg6757 -
Journal of Neurochemistry Apr 2021The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade,... (Review)
Review
The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade, presynaptic dysfunction has emerged as a key mediator of a series of neurodevelopmental and neurodegenerative disorders. This special issue will highlight some of the important presynaptic molecules and mechanisms that are disrupted in these conditions and reveal potential routes for therapy.
Topics: Animals; Humans; Neurodegenerative Diseases; Neurotransmitter Agents; Presynaptic Terminals; Synapses; Synaptic Vesicles
PubMed: 33728654
DOI: 10.1111/jnc.15319 -
Learning & Memory (Cold Spring Harbor,... May 2024The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we...
The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.
Topics: Animals; Mushroom Bodies; Presynaptic Terminals; Drosophila Proteins; Memory; rab3 GTP-Binding Proteins; Nerve Tissue Proteins; Drosophila; Synaptic Vesicles
PubMed: 38862173
DOI: 10.1101/lm.054013.124 -
Trends in Neurosciences Jun 2019Presynaptic boutons support neurotransmitter release with nanoscale precision at sub-millisecond timescales. Studies over the past two decades have revealed a rich... (Review)
Review
Presynaptic boutons support neurotransmitter release with nanoscale precision at sub-millisecond timescales. Studies over the past two decades have revealed a rich tapestry of molecular players governing synaptic vesicle fusion at highly specialized release sites in the active zone (AZ). However, the spatiotemporal organization of release at active synapses remains elusive, in part owing to the extremely small size of the AZ and the limited resolution of conventional approaches. Recent advances in fluorescence nanoscopy have revolutionized direct investigation of presynaptic release organization and dynamics. We discuss here recent nanoscopy-based studies of the molecular architecture, the spatial organization and dynamic regulation of release sites, and the mechanisms of release site replenishment. These findings have uncovered previously unknown levels of structural and functional organization at central synapses, with important implications for synaptic transmission and plasticity.
Topics: Animals; Exocytosis; Humans; Nanotechnology; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 31176424
DOI: 10.1016/j.tins.2019.03.001 -
Progress in Neurobiology Jul 2021To form and maintain extremely intricate and functional neural circuitry, mammalian neurons are typically endowed with highly arborized dendrites and a long axon. The... (Review)
Review
To form and maintain extremely intricate and functional neural circuitry, mammalian neurons are typically endowed with highly arborized dendrites and a long axon. The synapses that link neurons to neurons or to other cells are numerous and often too remote for the cell body to make and deliver new proteins to the right place in time. Moreover, synapses undergo continuous activity-dependent changes in their number and strength, establishing the basis of neural plasticity. The innate dilemma is then how a highly complex neuron provides new proteins for its cytoplasmic periphery and individual synapses to support synaptic plasticity. Here, we review a growing body of evidence that local protein synthesis in discrete sites of the axon and presynaptic terminals plays crucial roles in synaptic plasticity, and that deregulation of this local translation system is implicated in various pathologies of the nervous system.
Topics: Animals; Axons; Neuronal Plasticity; Neurons; Presynaptic Terminals; Synapses
PubMed: 33845165
DOI: 10.1016/j.pneurobio.2021.102051 -
Experimental Cell Research Jul 2015Actin is the most abundant cytoskeletal protein in presynaptic terminals as well as in postsynaptic dendritic spines of central excitatory synapses. While the relevance... (Review)
Review
Actin is the most abundant cytoskeletal protein in presynaptic terminals as well as in postsynaptic dendritic spines of central excitatory synapses. While the relevance of actin dynamics for postsynaptic plasticity, for instance activity-induced changes in dendritic spine morphology and synaptic glutamate receptor mobility, is well-documented, only little is known about its function and regulatory mechanisms in presynaptic terminals. Moreover, studies on presynaptic actin dynamics have often been inconsistent, suggesting that actin has diverse presynaptic functions, varying likely between specific types of excitatory synapses and/or their activity states. In this review, we will summarize and discuss the function and upstream regulatory mechanisms of the actin cytoskeleton in presynaptic terminals, focusing on excitatory synapses of the mammalian central nervous system. Due to length restrictions we will mainly concentrate on new insights into actin's presynaptic function that have been gained by cell biological and mouse genetic approaches since the excellent 2008 review by Cingolani and Goda.
Topics: Actin Cytoskeleton; Animals; Endocytosis; Exocytosis; Humans; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 25579398
DOI: 10.1016/j.yexcr.2014.12.020 -
FEBS Letters Nov 2018In presynaptic nerve terminals, synaptic vesicles are recycled locally via an evolutionarily conserved process that ensures maintenance of neurotransmission as well as... (Review)
Review
In presynaptic nerve terminals, synaptic vesicles are recycled locally via an evolutionarily conserved process that ensures maintenance of neurotransmission as well as structural integrity of synapses. Temperature is a key environmental factor that impacts critical steps involved in fusion, endocytosis and transport in different vesicle trafficking pathways. In neurons, temperature changes have been shown to impact synaptic vesicle recycling and synaptic efficacy. But contrary to non-neuronal systems, the temperature dependence of the steps involved in fusion, endocytosis and recycling of synaptic vesicles in presynaptic terminals is not completely understood, and the existing data remain highly debated. In this Review, we discuss the implications of biophysical, biochemical and functional findings on temperature dependence of membrane retrieval in multiple systems. We propose that systematic investigation of the temperature dependence of the presynaptic vesicle trafficking process can provide novel insight into poorly understood mechanisms that govern synaptic vesicle trafficking under diverse physiological conditions.
Topics: Animals; Endocytosis; Humans; Neurons; Presynaptic Terminals; Synapses; Synaptic Transmission; Synaptic Vesicles; Temperature; Time Factors
PubMed: 30311950
DOI: 10.1002/1873-3468.13268 -
Annual Review of Physiology 2015It is well established that the active properties of nerve and muscle cells are stabilized by homeostatic signaling systems. In organisms ranging from Drosophila to... (Review)
Review
It is well established that the active properties of nerve and muscle cells are stabilized by homeostatic signaling systems. In organisms ranging from Drosophila to humans, neurons restore baseline function in the continued presence of destabilizing perturbations by rebalancing ion channel expression, modifying neurotransmitter receptor surface expression and trafficking, and modulating neurotransmitter release. This review focuses on the homeostatic modulation of presynaptic neurotransmitter release, termed presynaptic homeostasis. First, we highlight criteria that can be used to define a process as being under homeostatic control. Next, we review the remarkable conservation of presynaptic homeostasis at the Drosophila, mouse, and human neuromuscular junctions and emerging parallels at synaptic connections in the mammalian central nervous system. We then highlight recent progress identifying cellular and molecular mechanisms. We conclude by reviewing emerging parallels between the mechanisms of homeostatic signaling and genetic links to neurological disease.
Topics: Animals; Drosophila; Homeostasis; Humans; Mice; Models, Animal; Neuromuscular Junction; Neuronal Plasticity; Neurotransmitter Agents; Presynaptic Terminals; Signal Transduction
PubMed: 25386989
DOI: 10.1146/annurev-physiol-021014-071740 -
Neuron Jan 2021Neurons are highly polarized cells with a single axon and multiple dendrites derived from the cell body to form tightly associated pre- and postsynaptic compartments. As... (Review)
Review
Neurons are highly polarized cells with a single axon and multiple dendrites derived from the cell body to form tightly associated pre- and postsynaptic compartments. As the biosynthetic machinery is largely restricted to the somatodendritic domain, the vast majority of presynaptic components are synthesized in the neuronal soma, packaged into synaptic precursor vesicles, and actively transported along the axon to sites of presynaptic biogenesis. In contrast with the significant progress that has been made in understanding synaptic transmission and processing of information at the post-synapse, comparably little is known about the formation and dynamic remodeling of the presynaptic compartment. We review here our current understanding of the mechanisms that govern the biogenesis, transport, and assembly of the key components for presynaptic neurotransmission, discuss how alterations in presynaptic assembly may impact nervous system function or lead to disease, and outline key open questions for future research.
Topics: Animals; Humans; Neurogenesis; Presynaptic Terminals; Protein Transport; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 33098763
DOI: 10.1016/j.neuron.2020.09.038 -
Nature Reviews. Neuroscience Jan 2018Synapses enable neurons to communicate with each other and are therefore a prerequisite for normal brain function. Presynaptically, this communication requires energy... (Review)
Review
Synapses enable neurons to communicate with each other and are therefore a prerequisite for normal brain function. Presynaptically, this communication requires energy and generates large fluctuations in calcium concentrations. Mitochondria are optimized for supplying energy and buffering calcium, and they are actively recruited to presynapses. However, not all presynapses contain mitochondria; thus, how might synapses with and without mitochondria differ? Mitochondria are also increasingly recognized to serve additional functions at the presynapse. Here, we discuss the importance of presynaptic mitochondria in maintaining neuronal homeostasis and how dysfunctional presynaptic mitochondria might contribute to the development of disease.
Topics: Animals; Calcium Signaling; Homeostasis; Humans; Mitochondria; Neurons; Presynaptic Terminals; Synaptic Transmission
PubMed: 29348666
DOI: 10.1038/nrn.2017.170