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International Journal of Molecular... May 2022Unrelated genetic mutations can lead to convergent manifestations of neurological disorders with similar behavioral phenotypes. Experimental data frequently show a lack... (Review)
Review
Unrelated genetic mutations can lead to convergent manifestations of neurological disorders with similar behavioral phenotypes. Experimental data frequently show a lack of dramatic changes in neuroanatomy, indicating that the key cause of symptoms might arise from impairment in the communication between neurons. A transient imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) synaptic transmission (the E/I balance) during early development is generally considered to underlie the development of several neurological disorders in adults. However, the E/I ratio is a multidimensional variable. Synaptic contacts are highly dynamic and the actual strength of synaptic projections is determined from the balance between synaptogenesis and synaptic elimination. During development, relatively slow postsynaptic receptors are replaced by fast ones that allow for fast stimulus-locked excitation/inhibition. Using the binomial model of synaptic transmission allows for the reassessing of experimental data from different mouse models, showing that a transient E/I shift is frequently counterbalanced by additional pre- and/or postsynaptic changes. Such changes-for instance, the slowing down of postsynaptic currents by means of immature postsynaptic receptors-stabilize the average synaptic strength, but impair the timing of information flow. Compensatory processes and/or astrocytic signaling may represent possible targets for medical treatments of different disorders directed to rescue the proper information processing.
Topics: Animals; Astrocytes; Excitatory Postsynaptic Potentials; Mice; Neurons; Signal Transduction; Synaptic Transmission
PubMed: 35628556
DOI: 10.3390/ijms23105746 -
Vitamins and Hormones 2020
Topics: Animals; Hormones; Synaptic Transmission
PubMed: 32723553
DOI: 10.1016/S0083-6729(20)30046-7 -
Neuropharmacology May 2023ATP released from the synaptic terminals and astrocytes can activate neuronal P2 receptors at a variety of locations across the CNS. Although the postsynaptic... (Review)
Review
ATP released from the synaptic terminals and astrocytes can activate neuronal P2 receptors at a variety of locations across the CNS. Although the postsynaptic ATP-mediated signalling does not bring a major contribution into the excitatory transmission, it is instrumental for slow and diffuse modulation of synaptic dynamics and neuronal firing in many CNS areas. Neuronal P2X and P2Y receptors can be activated by ATP released from the synaptic terminals, astrocytes and microglia and thereby can participate in the regulation of synaptic homeostasis and plasticity. There is growing evidence of importance of purinergic regulation of synaptic transmission in different physiological and pathological contexts. Here, we review the main mechanisms underlying the complexity and diversity of purinergic signalling and purinergic modulation in central neurons.
Topics: Adenosine Triphosphate; Receptors, Purinergic P2; Synapses; Signal Transduction; Synaptic Transmission; Sensory Receptor Cells
PubMed: 36841527
DOI: 10.1016/j.neuropharm.2023.109477 -
Current Opinion in Neurobiology Aug 2017Synaptic adhesion molecules have been extensively studied for their contribution to the regulation of synapse development through trans-synaptic adhesions. However,... (Review)
Review
Synaptic adhesion molecules have been extensively studied for their contribution to the regulation of synapse development through trans-synaptic adhesions. However, accumulating evidence increasingly indicates that synaptic adhesion molecules are also involved in the regulation of excitatory synaptic transmission and plasticity, often through direct or close associations with excitatory neurotransmitter receptors. This review summarizes recent results supporting this emerging concept and underlying mechanisms, and addresses its implications.
Topics: Animals; Cell Adhesion; Humans; Neuronal Plasticity; Synapses; Synaptic Transmission
PubMed: 28390263
DOI: 10.1016/j.conb.2017.03.005 -
Seminars in Cell & Developmental Biology May 2018
Topics: Cytoskeletal Proteins; Humans; Nerve Tissue Proteins; Neurons; Signal Transduction; Synaptic Transmission
PubMed: 29097154
DOI: 10.1016/j.semcdb.2017.10.027 -
Vitamins and Hormones 2020Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances... (Review)
Review
Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cellular and molecular mechanisms driving and governing transmitter release and sensing, the evolutionary origin of synaptic connections remains obscure. Herein, we review emerging evidence and concepts suggesting that key components of chemical synapse arose independently from neurons, in different functional and biological contexts, before the rise of multicellular living forms. We argue that throughout evolution, distinct synaptic constituents have been co-opted from ancestral forms for a new role in early metazoan, leading to the rise of chemical synapses and neurotransmission. Such a mosaic model of the origin of chemical synapses agrees with and supports the pluralistic hypothesis of evolutionary change.
Topics: Animals; Biological Evolution; Neurons; Synapses; Synaptic Transmission
PubMed: 32723540
DOI: 10.1016/bs.vh.2020.04.009 -
Neuroscience Bulletin Jan 2024Neuronomodulation refers to the modulation of neural conduction and synaptic transmission (i.e., the conduction process involved in synaptic transmission) of excitable... (Review)
Review
Neuronomodulation refers to the modulation of neural conduction and synaptic transmission (i.e., the conduction process involved in synaptic transmission) of excitable neurons via changes in the membrane potential in response to chemical substances, from spillover neurotransmitters to paracrine or endocrine hormones circulating in the blood. Neuronomodulation can be direct or indirect, depending on the transduction pathways from the ligand binding site to the ion pore, either on the same molecule, i.e. the ion channel, or through an intermediate step on different molecules. The major players in direct neuronomodulation are ligand-gated or voltage-gated ion channels. The key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels, either orthosterically or allosterically, by various ligands. Indirect neuronomodulation involves metabotropic receptor-mediated slow potentials, where steroid hormones, cytokines, and chemokines can implement these actions. Elucidating neuronomodulation is of great significance for understanding the physiological mechanisms of brain function, and the occurrence and treatment of diseases.
Topics: Ligands; Neurons; Synaptic Transmission; Ion Channels; Hormones
PubMed: 37584858
DOI: 10.1007/s12264-023-01095-w -
Neuron Oct 2023Neurons in the mammalian brain are not limited to releasing a single neurotransmitter but often release multiple neurotransmitters onto postsynaptic cells. Here, we... (Review)
Review
Neurons in the mammalian brain are not limited to releasing a single neurotransmitter but often release multiple neurotransmitters onto postsynaptic cells. Here, we review recent findings of multitransmitter neurons found throughout the mammalian central nervous system. We highlight recent technological innovations that have made the identification of new multitransmitter neurons and the study of their synaptic properties possible. We also focus on mechanisms and molecular constituents required for neurotransmitter corelease at the axon terminal and synaptic vesicle, as well as some possible functions of multitransmitter neurons in diverse brain circuits. We expect that these approaches will lead to new insights into the mechanism and function of multitransmitter neurons, their role in circuits, and their contribution to normal and pathological brain function.
Topics: Animals; Synaptic Transmission; Neurons; Brain; Central Nervous System; Neurotransmitter Agents; Glutamic Acid; Mammals
PubMed: 37463580
DOI: 10.1016/j.neuron.2023.06.003 -
ELife Dec 2021Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action...
Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action potential. Yet neurotransmitter release lacks a theoretical framework that is both phenomenologically accurate and mechanistically realistic. Here, we present an analytic theory of the action-potential-triggered neurotransmitter release at the chemical synapse. The theory is demonstrated to be in detailed quantitative agreement with existing data on a wide variety of synapses from electrophysiological recordings and fluorescence experiments . Despite up to ten orders of magnitude of variation in the release rates among the synapses, the theory reveals that synaptic transmission obeys a simple, universal scaling law, which we confirm through a collapse of the data from strikingly diverse synapses onto a single master curve. This universality is complemented by the capacity of the theory to readily extract, through a fit to the data, the kinetic and energetic parameters that uniquely identify each synapse. The theory provides a means to detect cooperativity among the SNARE complexes that mediate vesicle fusion and reveals such cooperativity in several existing data sets. The theory is further applied to establish connections between molecular constituents of synapses and synaptic function. The theory allows competing hypotheses of short-term plasticity to be tested and identifies the regimes where particular mechanisms of synaptic facilitation dominate or, conversely, fail to account for the existing data for the paired-pulse ratio. The derived trade-off relation between the transmission rate and fidelity shows how transmission failure can be controlled by changing the microscopic properties of the vesicle pool and SNARE complexes. The established condition for the maximal synaptic efficacy reveals that no fine tuning is needed for certain synapses to maintain near-optimal transmission. We discuss the limitations of the theory and propose possible routes to extend it. These results provide a quantitative basis for the notion that the molecular-level properties of synapses are crucial determinants of the computational and information-processing functions in synaptic transmission.
Topics: Action Potentials; Animals; Neurotransmitter Agents; Synapses; Synaptic Transmission
PubMed: 34970965
DOI: 10.7554/eLife.73585 -
Neuroscience Nov 2022Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for... (Review)
Review
Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for synaptic neurotransmission, the abnormalities of vesicle release and synaptic plasticity are associated with various neuropsychiatric disorders. Neural circuits are ensembles of interconnected neurons that collectively perform specific functions. To some extent, depression may be caused by a disruption in the structural and functional connections of the neural circuits underlying emotion regulation. In this review, we summarized the role of abnormalities of vesicle release and synaptic transmission, as well as the related regulatory molecules and signal pathways in the regulation of depression.
Topics: Synaptic Vesicles; Depression; Synaptic Transmission; Neurons; Neuronal Plasticity; Synapses
PubMed: 36228829
DOI: 10.1016/j.neuroscience.2022.10.001