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Philosophical Transactions of the Royal... Jan 2014Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is... (Review)
Review
Long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus has been investigated in great detail over the past 40 years. Where and how LTP is actually expressed, however, remain controversial issues. Considerable evidence has been offered to support both pre- and postsynaptic contributions to LTP expression. Though it is widely held that postsynaptic expression mechanisms are the primary contributors to LTP expression, evidence for that conclusion is amenable to alternative explanations. Here, we briefly review some key contributions to the 'locus' debate and describe data that support a dominant role for presynaptic mechanisms. Recognition of the state-dependency of expression mechanisms, and consideration of the consequences of the spatial relationship between postsynaptic glutamate receptors and presynaptic vesicular release sites, lead to a model that may reconcile views from both sides of the synapse.
Topics: Excitatory Postsynaptic Potentials; Glutamic Acid; Hippocampus; Humans; Long-Term Potentiation; Models, Neurological; Neurotransmitter Agents; Presynaptic Terminals
PubMed: 24298138
DOI: 10.1098/rstb.2013.0135 -
The Journal of Neuroscience : the... Sep 2020Multiple forms of homeostasis influence synaptic function under diverse activity conditions. Both presynaptic and postsynaptic forms of homeostasis are important, but...
Multiple forms of homeostasis influence synaptic function under diverse activity conditions. Both presynaptic and postsynaptic forms of homeostasis are important, but their relative impact on fidelity is unknown. To address this issue, we studied auditory nerve synapses onto bushy cells in the cochlear nucleus of mice of both sexes. These synapses undergo bidirectional presynaptic and postsynaptic homeostatic changes with increased and decreased acoustic stimulation. We found that both young and mature synapses exhibit similar activity-dependent changes in short-term depression. Experiments using chelators and imaging both indicated that presynaptic Ca influx decreased after noise exposure, and increased after ligating the ear canal. By contrast, Ca cooperativity was unaffected. Experiments using specific antagonists suggest that occlusion leads to changes in the Ca channel subtypes driving neurotransmitter release. Furthermore, dynamic-clamp experiments revealed that spike fidelity primarily depended on changes in presynaptic depression, with some contribution from changes in postsynaptic intrinsic properties. These experiments indicate that presynaptic Ca influx is homeostatically regulated to enhance synaptic fidelity. Homeostatic mechanisms in synapses maintain stable function in the face of different levels of activity. Both juvenile and mature auditory nerve synapses onto bushy cells modify short-term depression in different acoustic environments, which raises the question of what the underlying presynaptic mechanisms are and the relative importance of presynaptic and postsynaptic contributions to the faithful transfer of information. Changes in short-term depression under different acoustic conditions were a result of changes in presynaptic Ca influx. Spike fidelity was affected by both presynaptic and postsynaptic changes after ear occlusion and was only affected by presynaptic changes after noise-rearing. These findings are important for understanding regulation of auditory synapses under normal conditions and also in disorders following noise exposure or conductive hearing loss.
Topics: Animals; Auditory Perception; Calcium; Cochlear Nerve; Cochlear Nucleus; Female; Homeostasis; Male; Mice; Mice, Inbred CBA; Neuronal Plasticity; Noise; Presynaptic Terminals; Synaptic Potentials
PubMed: 32747441
DOI: 10.1523/JNEUROSCI.1175-19.2020 -
Current Opinion in Neurobiology Aug 2017Synaptic plasticity is critical for experience-dependent adjustments of brain function. While most research has focused on the mechanisms that underlie postsynaptic... (Review)
Review
Synaptic plasticity is critical for experience-dependent adjustments of brain function. While most research has focused on the mechanisms that underlie postsynaptic forms of plasticity, comparatively little is known about how neurotransmitter release is altered in a long-term manner. Emerging research suggests that many of the features of canonical 'postsynaptic' plasticity, such as associativity, structural changes and bidirectionality, also characterize long-term presynaptic plasticity. Recent studies demonstrate that presynaptic plasticity is a potent regulator of circuit output and function. Moreover, aberrant presynaptic plasticity is a convergent factor of synaptopathies like schizophrenia, addiction, and Autism Spectrum Disorders, and may be a potential target for treatment.
Topics: Brain; Humans; Mental Disorders; Neuronal Plasticity; Presynaptic Terminals; Synaptic Transmission
PubMed: 28570863
DOI: 10.1016/j.conb.2017.05.011 -
Journal of Neurochemistry Oct 2003The development of electrochemical recordings with small carbon-fiber electrodes has significantly advanced the understanding of the regulation of catecholamine... (Review)
Review
The development of electrochemical recordings with small carbon-fiber electrodes has significantly advanced the understanding of the regulation of catecholamine transmission in various brain areas. Recordings in vivo or in slice preparations monitor diffusion of catecholamine following stimulated synaptic release into the surrounding tissue. This synaptic 'overflow' is defined by the amount of release, by the activity of reuptake, and by the diffusion parameters in brain tissue. Such studies have elucidated the complex regulation of catecholamine release and uptake, and how psychostimulants and anti-psychotic drugs interfere with it. Moreover, recordings with carbon-fiber electrodes from cultured neurons have provided analysis of catecholamine release and its plasticity at the quantal level.
Topics: Animals; Catecholamines; Central Nervous System Stimulants; Dopamine; Electrophysiology; Humans; In Vitro Techniques; Microelectrodes; Neurons; Presynaptic Terminals; Synaptic Transmission
PubMed: 14511105
DOI: 10.1046/j.1471-4159.2003.02050.x -
Autophagy Sep 2020Maintaining the integrity and function of the presynaptic neurotransmitter release apparatus is a demanding process for a post-mitotic neuron; the mechanisms behind it...
Maintaining the integrity and function of the presynaptic neurotransmitter release apparatus is a demanding process for a post-mitotic neuron; the mechanisms behind it are still unclear. BSN (bassoon), an active zone scaffolding protein, has been implicated in the control of presynaptic macroautophagy/autophagy, a process we recently showed depends on poly-ubiquitination of synaptic proteins. Moreover, loss of BSN was found to lead to smaller synaptic vesicle (SV) pools and younger pools of the SV protein SV2. Of note, the E3 ligase PRKN/parkin appears to be involved in BSN deficiency-related changes in autophagy levels, as shRNA-mediated knockdown of PRKN counteracts BSN-deficiency and rescues decreased SV protein levels as well as impaired SV recycling in primary cultured neurons. These data imply that BSN and PRKN act in concert to control presynaptic autophagy and maintain presynaptic proteostasis and SV turnover at the physiologically required levels.
Topics: Animals; Autophagosomes; Autophagy; Mice; Nerve Tissue Proteins; Presynaptic Terminals; Synaptic Vesicles; Ubiquitin-Protein Ligases
PubMed: 32718208
DOI: 10.1080/15548627.2020.1801259 -
Neuron Feb 2011The fundamental principle that unites addictive drugs appears to be that each enhances synaptic dopamine by means that dissociate it from normal behavioral control, so... (Review)
Review
The fundamental principle that unites addictive drugs appears to be that each enhances synaptic dopamine by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. This occurs via the modulation of synaptic mechanisms that can be involved in learning, including enhanced excitation or disinhibition of dopamine neuron activity, blockade of dopamine reuptake, and altering the state of the presynaptic terminal to enhance evoked over basal transmission. Amphetamines offer an exception to such modulation in that they combine multiple effects to produce nonexocytic stimulation-independent release of neurotransmitter via reverse transport independent from normal presynaptic function. Questions about the molecular actions of addictive drugs, prominently including the actions of alcohol and solvents, remain unresolved, but their ability to co-opt normal presynaptic functions helps to explain why treatment for addiction has been challenging.
Topics: Amphetamines; Analgesics, Opioid; Animals; Central Nervous System Agents; Cocaine; Dopamine; Ethanol; Humans; Hypnotics and Sedatives; Models, Biological; Neural Inhibition; Neurons; Nicotine; Presynaptic Terminals; Synaptic Transmission
PubMed: 21338876
DOI: 10.1016/j.neuron.2011.02.010 -
Japanese Journal of Pharmacology Aug 1995Since the idea that memory is associated with alterations in synaptic strength was accepted, studies on the cellular and molecular mechanisms responsible for the plastic... (Review)
Review
Since the idea that memory is associated with alterations in synaptic strength was accepted, studies on the cellular and molecular mechanisms responsible for the plastic changes in neurons have attracted wide interest in the scientific community. Recent studies on memory processes have also pointed out some unifying themes emerging from a wide range of nervous systems, suggesting that regardless of the species or brain regions, a common denominator for memory may exist. Thus, the present review attempted to create a hypothetical and universal synaptic model valid for a variety of nervous systems, ranging from molluscs to mammals. The cellular and molecular events leading to short- and long-term modifications of memory have been described in a sequential order, from the triggering signals to the gene expression, synthesis of new proteins and neuronal growth. These events are thought to represent the late phases of memory consolidation leading to persistent modifications in synaptic plasticity, thereby facilitating the permanent storage of acquired information throughout the individual's life.
Topics: Animals; Memory; Models, Biological; Neural Pathways; Neuronal Plasticity; Presynaptic Terminals
PubMed: 8531412
DOI: 10.1254/jjp.68.359 -
Cell Reports Jan 2021Presynaptic action potential spikes control neurotransmitter release and thus interneuronal communication. However, the properties and the dynamics of presynaptic spikes...
Presynaptic action potential spikes control neurotransmitter release and thus interneuronal communication. However, the properties and the dynamics of presynaptic spikes in the neocortex remain enigmatic because boutons in the neocortex are small and direct patch-clamp recordings have not been performed. Here, we report direct recordings from boutons of neocortical pyramidal neurons and interneurons. Our data reveal rapid and large presynaptic action potentials in layer 5 neurons and fast-spiking interneurons reliably propagating into axon collaterals. For in-depth analyses, we establish boutons of mature cultured neurons as models for excitatory neocortical boutons, demonstrating that the presynaptic spike amplitude is unaffected by potassium channels, homeostatic long-term plasticity, and high-frequency firing. In contrast to the stable amplitude, presynaptic spikes profoundly broaden during high-frequency firing in layer 5 pyramidal neurons, but not in fast-spiking interneurons. Thus, our data demonstrate large presynaptic spikes and fundamental differences between excitatory and inhibitory boutons in the neocortex.
Topics: Electrophysiology; Humans; Neurons; Presynaptic Terminals; Synapses
PubMed: 33440142
DOI: 10.1016/j.celrep.2020.108612 -
Neuroscience Research Feb 2018Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a... (Review)
Review
Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones.
Topics: Aging; Animals; Humans; Mammals; Neuromuscular Diseases; Neuromuscular Junction; Presynaptic Terminals
PubMed: 29221906
DOI: 10.1016/j.neures.2017.11.014 -
Neuron Mar 2015Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression...
Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression.
Topics: Action Potentials; Animals; Axons; Patch-Clamp Techniques; Presynaptic Terminals; Purkinje Cells; Synapses
PubMed: 25789750
DOI: 10.1016/j.neuron.2015.03.006