-
The Journal of Neuroscience : the... Nov 2023Local protein synthesis in mature brain axons regulates the structure and function of presynaptic boutons by adjusting the presynaptic proteome to local demands. This...
Local protein synthesis in mature brain axons regulates the structure and function of presynaptic boutons by adjusting the presynaptic proteome to local demands. This crucial mechanism underlies experience-dependent modifications of brain circuits, and its dysregulation may contribute to brain disorders, such as autism and intellectual disability. Here, we discuss recent advancements in the axonal transcriptome, axonal RNA localization and translation, and the role of presynaptic local translation in synaptic plasticity and memory.
Topics: Axons; Presynaptic Terminals; Neuronal Plasticity; Brain
PubMed: 37940588
DOI: 10.1523/JNEUROSCI.1454-23.2023 -
Neuroscience Feb 2021In this review we will discuss the effect of two neuromodulatory transmitters, acetylcholine (ACh) and adenosine, on the synaptic release probability and short-term... (Review)
Review
In this review we will discuss the effect of two neuromodulatory transmitters, acetylcholine (ACh) and adenosine, on the synaptic release probability and short-term synaptic plasticity. ACh and adenosine differ fundamentally in the way they are released into the extracellular space. ACh is released mostly from synaptic terminals and axonal bouton of cholinergic neurons in the basal forebrain (BF). Its mode of action on synaptic release probability is complex because it activate both ligand-gated ion channels, so-called nicotinic ACh receptors and G-protein coupled muscarinic ACh receptors. In contrast, adenosine is released from both neurons and glia via nucleoside transporters or diffusion over the cell membrane in a non-vesicular, non-synaptic fashion; its receptors are exclusively G-protein coupled receptors. We show that ACh and adenosine effects are highly specific for an identified synaptic connection and depend mostly on the presynaptic but also on the postsynaptic receptor type and discuss the functional implications of these differences.
Topics: Acetylcholine; Cholinergic Agents; Presynaptic Terminals; Receptors, Muscarinic; Receptors, Nicotinic; Synaptic Transmission
PubMed: 32540364
DOI: 10.1016/j.neuroscience.2020.06.006 -
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 -
Molecules and Cells Nov 2015Synapsins were the first presynaptic proteins identified and have served as the flagship of the presynaptic protein field. Here we review recent studies demonstrating... (Review)
Review
Synapsins were the first presynaptic proteins identified and have served as the flagship of the presynaptic protein field. Here we review recent studies demonstrating that different members of the synapsin family play different roles at presynaptic terminals employing different types of synaptic vesicles. The structural underpinnings for these functions are just beginning to be understood and should provide a focus for future efforts.
Topics: Humans; Neurotransmitter Agents; Phosphorylation; Presynaptic Terminals; Protein Isoforms; Protein Transport; Synapsins; Synaptic Vesicles
PubMed: 26627875
DOI: 10.14348/molcells.2015.0233 -
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 -
The Journal of Neuroscience : the... Feb 2022Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of...
Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of their bioenergetic machinery to ensure these power demands are met, but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified. Here, we estimated the power demands of six motor nerve terminals in female larvae through direct measurements of neurotransmitter release and Ca entry, and via theoretical estimates of Na entry and power demands at rest. Electron microscopy revealed that terminals with the highest power demands contained the greatest volume of mitochondria, indicating that mitochondria are allocated according to presynaptic power demands. In addition, terminals with the greatest power demand-to-volume ratio (∼66 nmol·min·µl) harbor the largest mitochondria packed at the greatest density. If we assume sequential and complete oxidation of glucose by glycolysis and oxidative phosphorylation, then these mitochondria are required to produce ATP at a rate of 52 nmol·min·µl at rest, rising to 963 during activity. Glycolysis would contribute ATP at 0.24 nmol·min·µl of cytosol at rest, rising to 4.36 during activity. These data provide a quantitative framework for presynaptic bioenergetics , and reveal that, beyond an immediate capacity to accelerate ATP output from glycolysis and oxidative phosphorylation, over longer time periods presynaptic terminals optimize mitochondrial volume and density to meet power demand. The remarkable energy demands of the brain are supported by the complete oxidation of its fuel but debate continues regarding a division of labor between glycolysis and oxidative phosphorylation across different cell types. Here, we exploit the neuromuscular synapse, a model for studying neurophysiology, to elucidate fundamental aspects of neuronal energy metabolism that ultimately constrain rates of neural processing. We quantified energy production rates required to sustain activity at individual nerve terminals and compared these with the volume capable of oxidative phosphorylation (mitochondria) and glycolysis (cytosol). We find strong support for oxidative phosphorylation playing a primary role in presynaptic terminals and provide the first estimates of energy production rates per unit volume of presynaptic mitochondria and cytosol.
Topics: Animals; Brain; Drosophila; Energy Metabolism; Female; Mitochondria; Mitochondrial Size; Motor Neurons; Presynaptic Terminals; Synaptic Transmission
PubMed: 34907026
DOI: 10.1523/JNEUROSCI.1236-21.2021 -
Cell and Tissue Research Sep 2018The mammalian forebrain is constructed from ensembles of neurons that form local microcircuits giving rise to the exquisite cognitive tasks the mammalian brain can... (Review)
Review
The mammalian forebrain is constructed from ensembles of neurons that form local microcircuits giving rise to the exquisite cognitive tasks the mammalian brain can perform. Hippocampal neuronal circuits comprise populations of relatively homogenous excitatory neurons, principal cells and exceedingly heterogeneous inhibitory neurons, the interneurons. Interneurons release GABA from their axon terminals and are capable of controlling excitability in every cellular compartment of principal cells and interneurons alike; thus, they provide a brake on excess activity, control the timing of neuronal discharge and provide modulation of synaptic transmission. The dendritic and axonal morphology of interneurons, as well as their afferent and efferent connections within hippocampal circuits, is central to their ability to differentially control excitability, in a cell-type- and compartment-specific manner. This review aims to provide an up-to-date compendium of described hippocampal interneuron subtypes, with respect to their morphology, connectivity, neurochemistry and physiology, a full understanding of which will in time help to explain the rich diversity of neuronal function.
Topics: Animals; Cortical Excitability; Dendrites; Glutamic Acid; Hippocampus; Interneurons; Mice; Models, Neurological; Presynaptic Terminals; Rats; Synapses; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 30084021
DOI: 10.1007/s00441-018-2882-2 -
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 Aug 2020In a presynaptic nerve terminal, the active zone is composed of sophisticated protein machinery that enables secretion on a submillisecond time scale and precisely... (Review)
Review
In a presynaptic nerve terminal, the active zone is composed of sophisticated protein machinery that enables secretion on a submillisecond time scale and precisely targets it toward postsynaptic receptors. The past two decades have provided deep insight into the roles of active zone proteins in exocytosis, but we are only beginning to understand how a neuron assembles active zone protein complexes into effective molecular machines. In this review, we outline the fundamental processes that are necessary for active zone assembly and discuss recent advances in understanding assembly mechanisms that arise from genetic, morphological and biochemical studies. We further outline the challenges ahead for understanding this important problem.
Topics: Exocytosis; Neurons; Presynaptic Terminals; Proteins; Synapses
PubMed: 32403081
DOI: 10.1016/j.conb.2020.03.008 -
Proceedings of the National Academy of... Mar 2021For neuronal circuits in the brain to mature, necessary synapses must be maintained and redundant synapses eliminated through experience-dependent mechanisms. However,...
For neuronal circuits in the brain to mature, necessary synapses must be maintained and redundant synapses eliminated through experience-dependent mechanisms. However, the functional differentiation of these synapse types during the refinement process remains elusive. Here, we addressed this issue by distinct labeling and direct recordings of presynaptic terminals fated for survival and for elimination in the somatosensory thalamus. At surviving terminals, the number of total releasable vesicles was first enlarged, and then calcium channels and fast-releasing synaptic vesicles were tightly coupled in an experience-dependent manner. By contrast, transmitter release mechanisms did not mature at terminals fated for elimination, irrespective of sensory experience. Nonetheless, terminals fated for survival and for elimination both exhibited developmental shortening of action potential waveforms that was experience independent. Thus, we dissected experience-dependent and -independent developmental maturation processes of surviving and eliminated presynaptic terminals during neuronal circuit refinement.
Topics: Action Potentials; Afferent Pathways; Animals; Calcium Channels; Mice; Nerve Net; Neurotransmitter Agents; Presynaptic Terminals; Synaptic Vesicles; Trigeminal Nuclei; Ventral Thalamic Nuclei; Vibrissae
PubMed: 33688051
DOI: 10.1073/pnas.2022423118