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Current Neuropharmacology 2020General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many... (Review)
Review
General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention, including amnesia, hypnosis, analgesia, and immobility; while they may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand-gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions, including consciousness, memory, and cognition. Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity.
Topics: Anesthetics, General; Animals; Calcium Channels; Glutamic Acid; Humans; Isoflurane; Molecular Structure; Neuronal Plasticity; Neurons; Neurotransmitter Agents; Sodium; Synaptic Transmission; Voltage-Gated Sodium Channels; gamma-Aminobutyric Acid
PubMed: 32106800
DOI: 10.2174/1570159X18666200227125854 -
Autonomic Neuroscience : Basic &... Apr 2013Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise... (Review)
Review
Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise timing synaptic transmission. Since 2nd-order NTS neurons receiving baroreceptors inputs are relatively well characterized, their electrophysiological profile has been accepted as a general characteristic for all 2nd-order NTS neurons involved with the processing of different sensorial inputs. On the other hand, the synaptic properties of other afferent systems in NTS, such as the peripheral chemoreceptors, are not yet well understood. In this context, in previous studies we demonstrated that in response to repetitive afferents stimulation, the chemoreceptors 2nd-order NTS neurons also presented high fidelity of synaptic transmission, but with a large variability in the latency of evoked responses. This finding is different in relation to the precise timing transmission for baroreceptor 2nd-order NTS neurons, which was accepted as a general characteristic profile for all 2nd order neurons in the NTS. In this brief review we discuss this new concept as an index of complexity of the sensorial inputs to NTS with focus on the synaptic processing of baro- and chemoreceptor afferents.
Topics: Animals; Chemoreceptor Cells; Excitatory Postsynaptic Potentials; Humans; Neurons; Pressoreceptors; Solitary Nucleus; Synaptic Transmission
PubMed: 23305891
DOI: 10.1016/j.autneu.2012.12.002 -
Current Biology : CB Oct 1995The kinetics of different steps in synaptic-vesicle recycling, including exocytosis, internalization and repriming, have recently been estimated in various types of... (Review)
Review
The kinetics of different steps in synaptic-vesicle recycling, including exocytosis, internalization and repriming, have recently been estimated in various types of living cell.
Topics: Animals; Synaptic Transmission; Synaptic Vesicles; Time Factors
PubMed: 8548276
DOI: 10.1016/s0960-9822(95)00220-x -
STAR Protocols Mar 2022Spontaneous spiking activity depends on intrinsic excitability and synaptic input. Historically, synaptic activity has been mostly studied . Here, we describe a...
Spontaneous spiking activity depends on intrinsic excitability and synaptic input. Historically, synaptic activity has been mostly studied . Here, we describe a versatile and robust protocol to record field excitatory postsynaptic potentials (fEPSPs) in behaving rodents. The protocol allows estimating the input-output relationship of a specific pathway, short-term and long-term plasticity, and their modulation by pharmacological or pharmacogenetic interventions and behavioral states. However, experimenters must be aware of the protocol's specificity and interpret results with care. For complete details on the use and execution of this profile, please refer to Styr et al. (2019).
Topics: Animals; Excitatory Postsynaptic Potentials; Female; Male; Mice; Neuronal Plasticity; Synaptic Transmission
PubMed: 35118427
DOI: 10.1016/j.xpro.2021.101115 -
Arzneimittel-Forschung Feb 1992Beside the gamma-aminobutyric acid (GABA)-transporter and the GABAB-autoreceptor, the subsynaptic GABAA-receptor is therapeutically the most relevant target for drug... (Review)
Review
Beside the gamma-aminobutyric acid (GABA)-transporter and the GABAB-autoreceptor, the subsynaptic GABAA-receptor is therapeutically the most relevant target for drug actions influencing GABAergic synaptic transmission. New strategies in drug development focus on partial agonists acting at the benzodiazepine receptor. Since these compounds display less of the undesirable effects associated with the presently used full agonists, a major therapeutic advance is to be expected in the treatment of anxiety disorders and epilepsy. In addition, the extensive structural heterogeneity of GABAA-receptors, derived from a family of more than 15 subunits, may point to an unexpected functional heterogeneity of the receptor which may be exploited pharmacologically. The potential diversity of GABAA-receptor function is presently being analyzed using recombinant GABAA-receptors, which consist of various subunit combinations. These studies point not only to variations in the affinity of GABA, depending on the type of subunit combination, but also to differences in the affinities and intrinsic efficacies of benzodiazepine receptor ligands. Provided these distinctions can be confirmed at GABAA-receptors in situ, a new picture of the physiological and pharmacological regulation of the subsynaptic actions of GABA will emerge.
Topics: Animals; Humans; Synapses; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 1316752
DOI: No ID Found -
Scientific Reports Aug 2022Infrared (IR) neuromodulation (INM) has been demonstrated as a novel modulation modality of neuronal excitability. However, the effects of pulsed IR light on synaptic...
Infrared (IR) neuromodulation (INM) has been demonstrated as a novel modulation modality of neuronal excitability. However, the effects of pulsed IR light on synaptic transmission have not been investigated systematically. In this report, the IR light (2 μm) is used to directly modulate evoked synaptic transmission at the crayfish opener neuromuscular junction. The extracellularly recorded terminal action potentials (tAPs) and evoked excitatory postsynaptic currents (EPSCs) modulated by localized IR light illumination (500 ms, 3-13 mW) aimed at the synapses are analyzed. The impact of a single IR light pulse on the presynaptic Ca influx is monitored with Ca indicators. The EPSC amplitude is enhanced, and its rising phase is accelerated under relatively low IR light power levels and localized temperature rises. Increasing the IR light power reversibly suppresses and eventually blocks the EPSCs. Meanwhile, the synaptic delay, tAP amplitude, and presynaptic Ca influx decrease monotonously with higher IR light power. It is demonstrated for the first time that IR light illumination has bidirectional effects on evoked synaptic transmission. These results highlight the efficacy and flexibility of using pulsed IR light to directly control synaptic transmission and advance our understanding of INM of neural networks.
Topics: Action Potentials; Excitatory Postsynaptic Potentials; Neuromuscular Junction; Synapses; Synaptic Transmission
PubMed: 35987765
DOI: 10.1038/s41598-022-18139-2 -
Progress in Brain Research 1996
Review
Topics: Afferent Pathways; Animals; Neurons; Pain; Spinal Cord; Synaptic Transmission
PubMed: 9009750
DOI: No ID Found -
Headache 2003Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the... (Review)
Review
Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.
Topics: Acetylcholine; Animals; Botulinum Toxins; Exocytosis; Humans; Neuromuscular Junction; Synaptic Transmission; Time Factors
PubMed: 12887390
DOI: 10.1046/j.1526-4610.43.7s.4.x -
Frontiers in Neural Circuits 2016"Neuronal assemblies" are defined here as coalitions within the brain of millions of neurons extending in space up to 1-2 mm, and lasting for hundreds of milliseconds:... (Review)
Review
"Neuronal assemblies" are defined here as coalitions within the brain of millions of neurons extending in space up to 1-2 mm, and lasting for hundreds of milliseconds: as such they could potentially link bottom-up, micro-scale with top-down, macro-scale events. The perspective first compares the features versus of this underappreciated "meso-scale" level of brain processing, secondly considers the various diverse functions in which assemblies may play a pivotal part, and thirdly analyses whether the surprisingly spatially extensive and prolonged temporal properties of assemblies can be described exclusively in terms of classic synaptic transmission or whether additional, different types of signaling systems are likely to operate. Based on our own voltage-sensitive dye imaging (VSDI) data acquired we show how restriction to only one signaling process, i.e., synaptic transmission, is unlikely to be adequate for modeling the full profile of assemblies. Based on observations from VSDI with its protracted spatio-temporal scales, we suggest that two other, distinct processes are likely to play a significant role in assembly dynamics: "volume" transmission (the passive diffusion of diverse bioactive transmitters, hormones, and modulators), as well as electrotonic spread via gap junctions. We hypothesize that a combination of all three processes has the greatest potential for deriving a realistic model of assemblies and hence elucidating the various complex brain functions that they may mediate.
Topics: Animals; Gap Junctions; Nerve Net; Neurons; Synaptic Transmission
PubMed: 28119576
DOI: 10.3389/fncir.2016.00114 -
Current Biology : CB Aug 1998Recent studies suggest that transmitter molecules released at central synapses sometimes diffuse long enough distances to activate receptors located outside the synaptic... (Review)
Review
Recent studies suggest that transmitter molecules released at central synapses sometimes diffuse long enough distances to activate receptors located outside the synaptic cleft or even in neighboring synapses. This transmitter 'spillover' may have important physiological consequences.
Topics: Animals; Neurotransmitter Agents; Receptor Cross-Talk; Receptors, Glutamate; Synaptic Transmission
PubMed: 9742391
DOI: 10.1016/s0960-9822(98)70389-6