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Frontiers in Neural Circuits 2017Histamine H receptors are autoreceptors that regulate histamine release from histaminergic neuronal terminals. The cerebral cortex, including the insular cortex (IC),...
Histamine H receptors are autoreceptors that regulate histamine release from histaminergic neuronal terminals. The cerebral cortex, including the insular cortex (IC), expresses abundant H receptors; however, the functions and mechanisms of H receptors remain unknown. The aim of this study was to elucidate the functional roles of H in synaptic transmission in layer V of the rat IC. Unitary excitatory and inhibitory postsynaptic currents (uEPSCs and uIPSCs) were obtained through paired whole-cell patch-clamp recording in cerebrocortical slice preparations. The H receptor agonist, R-α-methylhistamine (RAMH), reduced the uEPSC amplitude obtained from pyramidal cell to pyramidal cell or GABAergic interneuron connections. Similarly, RAMH reduced the uIPSC amplitude in GABAergic interneuron to pyramidal cell connections. RAMH-induced decreases in both the uEPSC and uIPSC amplitudes were accompanied by increases in the failure rate and paired-pulse ratio. JNJ 5207852 dihydrochloride or thioperamide, H receptor antagonists, inhibited RAMH-induced suppression of uEPSCs and uIPSCs. Unexpectedly, thioperamide alone increased the uIPSC amplitude, suggesting that thioperamide was likely to act as an inverse agonist. Miniature EPSC or IPSC recordings support the hypothesis that the activation of H receptors suppresses the release of glutamate and GABA from presynaptic terminals. The colocalization of H receptors and glutamate decarboxylase or vesicular glutamate transport protein 1 in presynaptic axon terminals was confirmed through double pre-embedding microscopy, using a combination of pre-embedding immunogold and immunoperoxidase techniques. The suppressive regulation of H heteroreceptors on synaptic transmission might mediate the regulation of sensory information processes, such as gustation and visceral sensation, in the IC.
Topics: Animals; Axons; Cerebral Cortex; Excitatory Postsynaptic Potentials; Glutamic Acid; Histamine Agonists; Histamine Antagonists; Inhibitory Postsynaptic Potentials; Interneurons; Male; Miniature Postsynaptic Potentials; Pyramidal Cells; Rats, Sprague-Dawley; Rats, Transgenic; Receptors, Histamine H3; Synaptic Transmission; Tissue Culture Techniques; gamma-Aminobutyric Acid
PubMed: 29170631
DOI: 10.3389/fncir.2017.00085 -
The Journal of Neuroscience : the... Feb 2022Neurons regulate the strength of their synapses in response to a perturbation to stabilize neuronal signaling through a form of homeostatic plasticity known as synaptic...
Neurons regulate the strength of their synapses in response to a perturbation to stabilize neuronal signaling through a form of homeostatic plasticity known as synaptic scaling. The process of scaling has the potential to alter all of a cell's miniature postsynaptic current (mPSC) amplitudes by a single multiplicative factor (uniform scaling), and in doing so could change action potential-dependent or evoked synaptic strength by that factor. However, recent studies suggest that individual synapses scale with different scaling factors (nonuniform). This could complicate the simple multiplicative transform from mPSC scaling to the evoked response. We have previously identified a slow AMPAergic and GABAergic synaptic scaling in chick embryo motoneurons following 2 d perturbations inhibiting neuronal activity or GABAR function, and now show a rapid form of scaling following NMDAR blockade Slow GABAergic scaling appeared to be of a classical uniform pattern. Alternatively, other forms of rapid and slow scaling demonstrated a uniform and nonuniform component in their mPSC amplitude distributions. Slow and rapid AMPAergic scaling was mediated by insertion of GluA2-lacking AMPA receptors. The nonuniform pattern of scaling may contribute to the observed complexity of the changes in evoked responses. Scaling-induced changes in mPSC amplitudes were not associated with changes in probability of release (). Together, our results demonstrate a new rapid form of scaling in embryonic motoneurons, that slow and rapid scaling is not purely uniform, and that upscaling does not translate to an increase in evoked responses in a simple manner. Different forms of homeostatic plasticity are thought to play a critical role in maintaining neural function. For example, altering the amplitudes of spontaneous currents through a form of homeostatic plasticity known as synaptic scaling could affect evoked transmission; however, this is rarely tested. Here we demonstrate two forms of scaling and show that in many cases synaptic strength scales differently for distinct synapses within an embryonic motoneuron. These results have functional consequences for evoked synaptic strength and suggest that, like Hebbian plasticity, scaling can change relative synaptic strengths within a cell. Furthermore, our results demonstrate how different forms of homeostatic plasticity influence neuronal communication as the nascent spinal network is first established in the embryonic period.
Topics: Animals; Chick Embryo; Homeostasis; Motor Neurons; Neurogenesis; Neuronal Plasticity; Synaptic Potentials; Synaptic Transmission
PubMed: 34965976
DOI: 10.1523/JNEUROSCI.0899-21.2021 -
Progress in Neuro-psychopharmacology &... Nov 2009Glutamate, catecholamine and neuropeptide signaling within the bed nucleus of the stria terminalis (BNST) have all been identified as key participants in anxiety-like... (Review)
Review
Glutamate, catecholamine and neuropeptide signaling within the bed nucleus of the stria terminalis (BNST) have all been identified as key participants in anxiety-like behaviors and behaviors related to withdrawal from exposure to substances of abuse. The BNST is thought to serve as a key relay between limbic cognitive centers and reward, stress and anxiety nuclei. Human studies and animal models have demonstrated that stressors and drugs of abuse can result in long term behavioral modifications that can culminate in psychological diseases such as addiction and post-traumatic stress disorder. The ability of catecholamines and neuropeptides to influence synaptic glutamatergic transmission (stemming from cognitive centers) within the BNST may have profound consequences over these behaviors. In this review we highlight studies examining synaptic plasticity and modulation of excitatory transmission within the BNST, emphasizing how such modulation may result in alterations in anxiety and reward related behavior.
Topics: Animals; Anxiety; Glutamic Acid; Humans; Neuronal Plasticity; Neurons; Reward; Septal Nuclei; Synapses; Synaptic Transmission
PubMed: 19524008
DOI: 10.1016/j.pnpbp.2009.05.022 -
Current Opinion in Neurobiology Dec 2021The primary function common to every neuron is communication with other neurons. Such cell-cell signaling can take numerous forms, including fast synaptic transmission... (Review)
Review
The primary function common to every neuron is communication with other neurons. Such cell-cell signaling can take numerous forms, including fast synaptic transmission and slower neuromodulation via secreted messengers, such as neuropeptides, dopamine, and many other diffusible small molecules. Individual neurons are quite diverse, however, in all particulars of both synaptic and neuromodulatory communication. Neuron classification schemes have therefore proven very useful in exploring the emergence of network function, behavior, and cognition from the communication functions of individual neurons. Recently published single-cell mRNA sequencing data and corresponding transcriptomic neuron classifications from turtle, songbird, mouse, and human provide evidence for a long evolutionary history and adaptive significance of localized peptidergic signaling. Across all four species, sets of at least twenty orthologous cognate pairs of neuropeptide precursor protein and receptor genes are expressed in individually sparse but heavily overlapping patterns suggesting that all forebrain neuron types are densely interconnected by local peptidergic signals.
Topics: Animals; Humans; Neurons; Neuropeptides; Prosencephalon; Synaptic Transmission; Transcriptome
PubMed: 34775262
DOI: 10.1016/j.conb.2021.09.011 -
Current Psychiatry Reports Aug 2017Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose... (Review)
Review
PURPOSE OF REVIEW
Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.
RECENT FINDINGS
Here, we will briefly review evidence that PTSD might be a "synaptic disconnection syndrome" and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.
Topics: Animals; Disease Models, Animal; Excitatory Amino Acid Antagonists; Humans; Ketamine; Neurobiology; Stress Disorders, Post-Traumatic; Synaptic Transmission
PubMed: 28844076
DOI: 10.1007/s11920-017-0829-z -
Neuron Sep 2014Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are... (Review)
Review
Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are often attained upon the refinement of early, less precise connectivity. Much work has led to the prevailing view that many developing circuits are sculpted by activity-dependent competition among converging afferents, which results in the elimination of unwanted synapses and the maintenance and strengthening of desired connections. Studies of the vertebrate retina, however, have recently revealed that activity can play a role in shaping developing circuits without engaging competition among converging inputs that differ in their activity levels. Such neurotransmission-mediated processes can produce stereotypic wiring patterns by promoting selective synapse formation rather than elimination. We discuss how the influence of transmission may also be limited by circuit design and further highlight the importance of transmission beyond development in maintaining wiring specificity and synaptic organization of neural circuits.
Topics: Animals; Humans; Neural Pathways; Neurons; Synaptic Transmission
PubMed: 25233313
DOI: 10.1016/j.neuron.2014.08.029 -
Neuron May 2016The mechanism and speed of endocytosis at central synapses after neurotransmitter release is still under debate. In this issue of Neuron,Delvendahl et al. (2016)... (Review)
Review
The mechanism and speed of endocytosis at central synapses after neurotransmitter release is still under debate. In this issue of Neuron,Delvendahl et al. (2016) propose an ultrafast form of endocytosis after single action potentials (APs) at physiological temperature.
Topics: Action Potentials; Animals; Endocytosis; Excitatory Postsynaptic Potentials; Humans; Neurons; Synapses; Synaptic Transmission
PubMed: 27151632
DOI: 10.1016/j.neuron.2016.04.027 -
Essays in Biochemistry Mar 2023Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into the neuropil, where they interact...
Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into the neuropil, where they interact with a variety of other cell types, including neurons at synapses. Astrocytes are now known to be active players in all aspects of the synaptic life cycle, including synapse formation and elimination, synapse maturation, maintenance of synaptic homeostasis and modulation of synaptic transmission. Traditionally, astrocytes have been studied as a homogeneous group of cells. However, recent studies have uncovered a surprising degree of heterogeneity in their development and function, suggesting that astrocytes may be matched to neurons to support local circuits. Hence, a better understanding of astrocyte heterogeneity and its implications are needed to understand brain function.
Topics: Astrocytes; Synaptic Transmission; Synapses; Neurons; Central Nervous System
PubMed: 36748397
DOI: 10.1042/EBC20220136 -
Current Opinion in Neurobiology Apr 2000Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in... (Review)
Review
Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity--postsynaptic bursting--accompanies synaptic potentiation in adults.
Topics: Action Potentials; Animals; Computer Simulation; Excitatory Postsynaptic Potentials; Hippocampus; Humans; Learning; Long-Term Potentiation; Neuronal Plasticity; Rats; Synaptic Transmission
PubMed: 10753798
DOI: 10.1016/s0959-4388(00)00076-3 -
ENeuro 2019Tau is a highly soluble microtubule-associated protein that acts within neurons to modify microtubule stability. However, abnormally phosphorylated tau dissociates from...
Tau is a highly soluble microtubule-associated protein that acts within neurons to modify microtubule stability. However, abnormally phosphorylated tau dissociates from microtubules to form oligomers and fibrils which associate in the somatodendritic compartment. Although tau can form neurofibrillary tangles (NFTs), it is the soluble oligomers that appear to be the toxic species. There is, however, relatively little quantitative information on the concentration-dependent and time-dependent actions of soluble tau oligomers (oTau) on the electrophysiological and synaptic properties of neurons. Here, whole-cell patch clamp recording was used to introduce known concentrations of oligomeric full-length tau-441 into mouse hippocampal CA1 pyramidal and neocortical Layer V thick-tufted pyramidal cells. oTau increased input resistance, reduced action potential amplitude and slowed action potential rise and decay kinetics. oTau injected into presynaptic neurons induced the run-down of unitary EPSPs which was associated with increased short-term depression. In contrast, introduction of oTau into postsynaptic neurons had no effect on basal synaptic transmission, but markedly impaired the induction of long-term potentiation (LTP). Consistent with its effects on synaptic transmission and plasticity, oTau puncta could be observed in the soma, axon and in the distal dendrites of injected neurons.
Topics: Action Potentials; Animals; Cerebral Cortex; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Pyramidal Cells; Synaptic Transmission; tau Proteins
PubMed: 31554666
DOI: 10.1523/ENEURO.0166-19.2019