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ACS Chemical Neuroscience Sep 2014Neurotransmitter vesicles are known to concentrate hydrogen ions (or protons), the simplest ion, and to release them during neurotransmission. Furthermore, receptors... (Review)
Review
Neurotransmitter vesicles are known to concentrate hydrogen ions (or protons), the simplest ion, and to release them during neurotransmission. Furthermore, receptors highly sensitive to protons, acid-sensing ion channels (ASICs), were previously localized on the opposite side of the synaptic cleft on dendritic spines. Now, recent experiments provide some of the strongest support to date that protons function as a neurotransmitter in mice, crossing synapses onto medium spiny neurons of the nucleus accumbens (NAc), activating ASICs, and ultimately suppressing drug abuse-related behaviors.
Topics: Acid Sensing Ion Channels; Animals; Humans; Mice; Models, Biological; Neurotransmitter Agents; Protons; Substance-Related Disorders; Synaptic Transmission
PubMed: 25054738
DOI: 10.1021/cn500154w -
Current Opinion in Neurobiology Aug 2017It is firmly established that many mammalian neurons release various combinations of amino acids, their derivatives, and other small molecules from presynaptic terminals... (Review)
Review
It is firmly established that many mammalian neurons release various combinations of amino acids, their derivatives, and other small molecules from presynaptic terminals in order to signal to their postsynaptic targets. Here we discuss recent findings about four types of multi-transmitter neurons-those that release GABA and acetylcholine (Ach); dopamine (DA) and GABA or glutamate; and glutamate and GABA. The mechanisms of co-release in each class differ and highlight the complex and dynamic nature of neurotransmitter release. Furthermore, identifying the neurotransmitter signature of each neuron and the post-synaptic targets of each neurotransmitter remain challenging. The existence of multi-transmitter neurons complicates the interpretation of connectomic wiring diagrams and poses interesting challenges for our understanding of circuit function in the brain.
Topics: Animals; Central Nervous System; Mammals; Neurons; Synaptic Transmission
PubMed: 28500992
DOI: 10.1016/j.conb.2017.04.007 -
Neuron Feb 2005In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentials arise from a pool of vesicles distinct from those released by neural... (Review)
Review
In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentials arise from a pool of vesicles distinct from those released by neural activity. This modification of a basic tenet of the quantal hypothesis has important implications for the analysis of changes in synaptic transmission.
Topics: Animals; Animals, Genetically Modified; Models, Biological; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 15721234
DOI: 10.1016/j.neuron.2005.02.003 -
Respiratory Physiology & Neurobiology Oct 2011Respiratory motoneurons provide the exclusive drive to respiratory muscles and therefore are a key relay between brainstem neural circuits that generate respiratory... (Review)
Review
Respiratory motoneurons provide the exclusive drive to respiratory muscles and therefore are a key relay between brainstem neural circuits that generate respiratory rhythm and respiratory muscles that control moment of gases into and out of the airways and lungs. This review is focused on postnatal development of fast ionotropic synaptic transmission to respiratory motoneurons, with a focus on hypoglossal motoneurons (HMs). Glutamatergic synaptic transmission to HMs involves activation of both non-NMDA and NMDA receptors and during the postnatal period co-activation of these receptors located at the same synapse may occur. Further, the relative role of each receptor type in inspiratory-phase motoneuron depolarization is dependent on the type of preparation used (in vitro versus in vivo; neonatal versus adult). Respiratory motoneurons receive both glycinergic and GABAergic inhibitory synaptic inputs. During inspiration phrenic and HMs receive concurrent excitatory and inhibitory synaptic inputs. During postnatal development in HMs GABAergic and glycinergic synaptic inputs have slow kinetics and are depolarizing and with postnatal development they become faster and hyperpolarizing. Additionally shunting inhibition may play an important role in synaptic processing by respiratory motoneurons.
Topics: Animals; Humans; Motor Neurons; Respiratory Mechanics; Respiratory Muscles; Synaptic Transmission
PubMed: 21382524
DOI: 10.1016/j.resp.2011.03.002 -
The Journal of Physiology Jan 2012The time course of excitatory synaptic currents, the major means of fast communication between neurons of the central nervous system, is encoded in the dynamic behaviour... (Review)
Review
The time course of excitatory synaptic currents, the major means of fast communication between neurons of the central nervous system, is encoded in the dynamic behaviour of post-synaptic glutamate-activated channels. First-pass attempts to explain the glutamate-elicited currents with mathematical models produced reaction mechanisms that included only the most basic functionally defined states: resting vs. liganded, closed vs. open, responsive vs. desensitized. In contrast, single-molecule observations afforded by the patch-clamp technique revealed an unanticipated kinetic multiplicity of transitions: from microseconds-lasting flickers to minutes-long modes. How these kinetically defined events impact the shape of the synaptic response, how they relate to rearrangements in receptor structure, and whether and how they are physiologically controlled represent currently active research directions. Modal gating, which refers to the slowest, least frequently observed ion-channel transitions, has been demonstrated for representatives of all ion channel families. However, reaction schemes have been largely confined to the short- and medium-range time scales. For glutamate receptors as well, modal gating has only recently come under rigorous scrutiny. This article reviews the evidence for modal gating of glutamate receptors and the still developing hypotheses about the mechanism(s) by which modal shifts occur and the ways in which they may impact the time course of synaptic transmission.
Topics: Animals; Humans; Ion Channel Gating; Neurons; Receptors, Glutamate; Synaptic Potentials; Synaptic Transmission
PubMed: 22106181
DOI: 10.1113/jphysiol.2011.223750 -
Physiological Reports Oct 2019The central nucleus of the amygdala (CeA) is a primarily GABAergic brain region implicated in stress and addictive disorders. Using in vitro slice electrophysiology,...
The central nucleus of the amygdala (CeA) is a primarily GABAergic brain region implicated in stress and addictive disorders. Using in vitro slice electrophysiology, many studies measure GABAergic neurotransmission to evaluate the impact of experimental manipulations on inhibitory tone in the CeA, as a measure of alterations in CeA activity and function. In a recent study, we reported spontaneous inhibitory postsynaptic current (sIPSC) frequencies higher than those typically reported in CeA neurons in the literature, despite utilizing similar recording protocols and internal recording solutions. The purpose of this study was to systematically evaluate two common methods of slice preparation, an NMDG-based aCSF perfusion method and an ice-cold sucrose solution, as well as the use of an in-line heater to control recording temperature, on measures of intrinsic excitability and spontaneous inhibitory neurotransmission in CeA neurons. We report that both slice preparation and recording conditions significantly impact spontaneous GABAergic transmission in CeA neurons, and that recording temperature, but not slicing solution, alters measures of intrinsic excitability in CeA neurons. Bath application of corticotropin-releasing factor (CRF) increased sIPSC frequency under all conditions, but the magnitude of this effect was significantly different across recording conditions that elicited different baseline GABAergic transmission. Furthermore, CRF effects on synaptic transmission differed according to data reporting methods (i.e., raw vs. normalized data), which is important to consider in relation to baseline synaptic transmission values. These studies highlight the impact of experimental conditions and data reporting methods on neuronal excitability and synaptic transmission in the CeA.
Topics: Animals; Central Amygdaloid Nucleus; GABAergic Neurons; Inhibitory Postsynaptic Potentials; Male; Organ Culture Techniques; Rats; Rats, Wistar; Synaptic Transmission
PubMed: 31587506
DOI: 10.14814/phy2.14245 -
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 -
Proceedings of the National Academy of... May 2021Transcriptional dysregulation in Huntington's disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-sequencing (Patch-seq) in an in vitro...
Transcriptional dysregulation in Huntington's disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-sequencing (Patch-seq) in an in vitro HD model to investigate the effects of mutant Huntingtin (Htt) on synaptic transmission and gene transcription in single striatal neurons. We found that expression of mutant decreased the synaptic output of striatal neurons in a cell autonomous fashion and identified a number of genes whose dysregulation was correlated with physiological deficiencies in mutant Htt neurons. In support of a pivotal role for epigenetic mechanisms in HD pathophysiology, we found that inhibiting histone deacetylase 1/3 activities rectified several functional and morphological deficits and alleviated the aberrant transcriptional profiles in mutant Htt neurons. With this study, we demonstrate that Patch-seq technology can be applied both to better understand molecular mechanisms underlying a complex neurological disease at the single-cell level and to provide a platform for screening for therapeutics for the disease.
Topics: Animals; Benzamides; Corpus Striatum; Disease Models, Animal; GABA Agents; Gene Expression; Huntingtin Protein; Huntington Disease; Mice; Mice, Inbred C57BL; Neurons; Sequence Analysis, RNA; Synaptic Transmission; Transcriptome
PubMed: 33952696
DOI: 10.1073/pnas.2020293118 -
Current Opinion in Neurobiology Jun 2022Synaptic strength is thought to be determined by the number of presynaptic release sites, release probability and postsynaptic response to quantal release. Changes in... (Review)
Review
Synaptic strength is thought to be determined by the number of presynaptic release sites, release probability and postsynaptic response to quantal release. Changes in these parameters are directly relevant to synaptic plasticity. However, our understanding of these determinants as they relate to synaptic function has been reformed by recent work on nanoscale organizations of synaptic proteins. Specifically, release probability is distributed heterogeneously among multiple release sites within a single active zone, and the quantal postsynaptic response depends strongly on the local distribution of receptors around the release site. These nanoscale characteristics reveal a new deeper layer of modulation of synaptic transmission and plasticity.
Topics: Neuronal Plasticity; Synapses; Synaptic Transmission
PubMed: 35398662
DOI: 10.1016/j.conb.2022.102540 -
Cerebral Cortex (New York, N.Y. : 1991) Sep 2017Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wave sleep through inhibition of the brain's arousal centers. However, little is...
Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wave sleep through inhibition of the brain's arousal centers. However, little is known about the effect of adenosine on neuronal network activity at the cellular level in the neocortex. Here, we show that adenosine differentially modulates synaptic transmission between different types of neurons in cortical layer 4 (L4) through activation of pre- and/or postsynaptically located adenosine A1 receptors. In recurrent excitatory connections between L4 spiny neurons, adenosine suppresses synaptic transmission through activation of both pre- and postsynaptic A1 receptors. In reciprocal excitatory and inhibitory connections between L4 spiny neurons and interneurons, adenosine strongly suppresses excitatory transmission via activating presynaptic A1 receptors but only slightly suppresses inhibitory transmission via activating postsynaptic A1 receptors. Adenosine has no effect on inhibitory transmission between L4 interneurons. The effect of adenosine is concentration dependent and first visible at a concentration of 1 μM. The effect of adenosine is blocked by the specific A1 receptor antagonist, 8-cyclopentyltheophylline or the nonspecific adenosine receptor antagonist, caffeine. By differentially affecting excitatory and inhibitory synaptic transmission, adenosine changes the excitation-inhibition balance and causes an overall shift to lower excitability in L4 primary somatosensory (barrel) cortical microcircuits.
Topics: Adenosine; Animals; Excitatory Postsynaptic Potentials; Interneurons; Pyramidal Cells; Rats, Wistar; Receptor, Adenosine A1; Sleep; Somatosensory Cortex; Synapses; Synaptic Transmission
PubMed: 27522071
DOI: 10.1093/cercor/bhw243