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The FEBS Journal Nov 2020The cerebellum, a universal processor for sensory acquisition and internal models, and its association with synaptic and nonsynaptic plasticity have been envisioned as... (Review)
Review
The cerebellum, a universal processor for sensory acquisition and internal models, and its association with synaptic and nonsynaptic plasticity have been envisioned as the biological correlates of learning, perception, and even thought. Indeed, the cerebellum is no longer considered merely as the locus of motor coordination and its learning. Here, we introduce the mechanisms underlying the induction of multiple types of plasticity in cerebellar circuit and give an overview focusing on the plasticity of nonsynaptic intrinsic excitability. The discovery of long-term potentiation of synaptic responsiveness in hippocampal neurons led investigations into changes of their intrinsic excitability. This activity-dependent potentiation of neuronal excitability is distinct from that of synaptic efficacy. Systematic examination of excitability plasticity has indicated that the modulation of various types of Ca - and voltage-dependent K channels underlies the phenomenon, which is also triggered by immune activity. Intrinsic plasticity is expressed specifically on dendrites and modifies the integrative processing and filtering effect. In Purkinje cells, modulation of the discordance of synaptic current on soma and dendrite suggested a novel type of cellular learning mechanism. This property enables a plausible synergy between synaptic efficacy and intrinsic excitability, by amplifying electrical conductivity and influencing the polarity of bidirectional synaptic plasticity. Furthermore, the induction of intrinsic plasticity in the cerebellum correlates with motor performance and cognitive processes, through functional connections from the cerebellar nuclei to neocortex and associated regions: for example, thalamus and midbrain. Taken together, recent advances in neuroscience have begun to shed light on the complex functioning of nonsynaptic excitability and the synergy.
Topics: Animals; Cerebellum; Cerebral Cortex; Excitatory Postsynaptic Potentials; Hippocampus; Humans; Long-Term Potentiation; Neuronal Plasticity; Neurons; Synaptic Transmission
PubMed: 32367676
DOI: 10.1111/febs.15355 -
Journal of Alzheimer's Disease : JAD 2017Alzheimer's disease (AD) is a chronic neurodegenerative disorder, in which multiple risk factors converge. Despite the complexity of the etiology of the disease,... (Review)
Review
Alzheimer's disease (AD) is a chronic neurodegenerative disorder, in which multiple risk factors converge. Despite the complexity of the etiology of the disease, synaptic failure is the pathological basis of cognitive impairment, the cardinal sign of AD. Decreased synaptic density, compromised synaptic transmission, and defected synaptic plasticity are hallmark synaptic pathologies accompanying AD. However, the mechanisms by which synapses are injured in AD-related conditions have not been fully elucidated. Mitochondria are a critical organelle in neurons. The pivotal role of mitochondria in supporting synaptic function and the concomitant occurrence of mitochondrial dysfunction with synaptic stress in postmortem AD brains as well as AD animal models seem to lend the credibility to the hypothesis that mitochondrial defects underlie synaptic failure in AD. This concept is further strengthened by the protective effect of mitochondrial medicine on synaptic function against the toxicity of amyloid-β, a key player in the pathogenesis of AD. In this review, we focus on the association between mitochondrial dysfunction and synaptic transmission deficits in AD. Impaired mitochondrial energy production, deregulated mitochondrial calcium handling, excess mitochondrial reactive oxygen species generation and release play a crucial role in mediating synaptic transmission deregulation in AD. The understanding of the role of mitochondrial dysfunction in synaptic stress may lead to novel therapeutic strategies for the treatment of AD through the protection of synaptic transmission by targeting to mitochondrial deficits.
Topics: Alzheimer Disease; Animals; Humans; Mitochondria; Mitochondrial Diseases; Synaptic Transmission
PubMed: 27662318
DOI: 10.3233/JAD-160702 -
BMC Cell Biology May 2016Electrical synapses are an omnipresent feature of nervous systems, from the simple nerve nets of cnidarians to complex brains of mammals. Formed by gap junction channels... (Review)
Review
Electrical synapses are an omnipresent feature of nervous systems, from the simple nerve nets of cnidarians to complex brains of mammals. Formed by gap junction channels between neurons, electrical synapses allow direct transmission of voltage signals between coupled cells. The relative simplicity of this arrangement belies the sophistication of these synapses. Coupling via electrical synapses can be regulated by a variety of mechanisms on times scales ranging from milliseconds to days, and active properties of the coupled neurons can impart emergent properties such as signal amplification, phase shifts and frequency-selective transmission. This article reviews the biophysical characteristics of electrical synapses and some of the core mechanisms that control their plasticity in the vertebrate central nervous system.
Topics: Animals; Electric Conductivity; Electrical Synapses; Humans; Neuronal Plasticity; Signal Transduction; Synaptic Transmission
PubMed: 27230893
DOI: 10.1186/s12860-016-0091-y -
Journal of Neurochemistry Aug 2017This special issue is a companion to the meeting 'XVth International Symposium on Cholinergic Mechanisms', and is edited by Israel Silman, Marco Prado and Pascale... (Review)
Review
This special issue is a companion to the meeting 'XVth International Symposium on Cholinergic Mechanisms', and is edited by Israel Silman, Marco Prado and Pascale Marchot. In the review articles, renowned researchers in the field capture key mechanisms of cholinergic neurotransmission, from genomic amplification of cholinesterase genes, splicing and post-translational modifications; features of the neuromuscular junction, implications of cholinergic circuitry that are relevant to addiction, anxiety and mood, to preclinical models, protein biomarkers, and clinical findings that are relevant to pathology, for example, developmental neurotoxicity. The broad variety of features reflects the impact of cholinergic mechanisms on many physiological events and emphasizes the importance of research in this area. This is the Preface for the special issue XVth International Symposium on Cholinergic Mechanisms.
Topics: Acetylcholine; Animals; Behavior, Addictive; Cholinergic Agents; Humans; Neuromuscular Junction; Neurotoxicity Syndromes; Synaptic Transmission
PubMed: 28791707
DOI: 10.1111/jnc.14027 -
Advances in Experimental Medicine and... 2017We focus on dynamical descriptions of short-term synaptic plasticity. Instead of focusing on the molecular machinery that has been reviewed recently by several authors,... (Review)
Review
We focus on dynamical descriptions of short-term synaptic plasticity. Instead of focusing on the molecular machinery that has been reviewed recently by several authors, we concentrate on the dynamics and functional significance of synaptic plasticity, and review some mathematical models that reproduce different properties of the dynamics of short term synaptic plasticity that have been observed experimentally. The complexity and shortcomings of these models point to the need of simple, yet physiologically meaningful models. We propose a simplified model to be tested in synapses displaying different types of short-term plasticity.
Topics: Animals; Brain; Humans; Models, Neurological; Models, Theoretical; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 29080020
DOI: 10.1007/978-3-319-62817-2_3 -
Current Opinion in Neurobiology Feb 2019The probabilistic nature of synaptic transmission has remained enigmatic. However, recent developments have started to shed light on why the brain may rely on... (Review)
Review
The probabilistic nature of synaptic transmission has remained enigmatic. However, recent developments have started to shed light on why the brain may rely on probabilistic synapses. Here, we start out by reviewing experimental evidence on the specificity and plasticity of synaptic response statistics. Next, we overview different computational perspectives on the function of plastic probabilistic synapses for constrained, statistical and deep learning. We highlight that all of these views require some form of optimisation of probabilistic synapses, which has recently gained support from theoretical analysis of long-term synaptic plasticity experiments. Finally, we contrast these different computational views and propose avenues for future research. Overall, we argue that the time is ripe for a better understanding of the computational functions of probabilistic synapses.
Topics: Animals; Brain; Computer Simulation; Learning; Models, Neurological; Synapses; Synaptic Transmission
PubMed: 30308457
DOI: 10.1016/j.conb.2018.09.002 -
Current Opinion in Neurobiology Dec 2014Neuromodulation underlies the flexibility of neural circuit operation and behavior. Individual neuromodulators can have divergent actions in a neuron by targeting... (Review)
Review
Neuromodulation underlies the flexibility of neural circuit operation and behavior. Individual neuromodulators can have divergent actions in a neuron by targeting multiple physiological mechanisms. Conversely, multiple neuromodulators may have convergent actions through overlapping targets. The divergent and convergent neuromodulator actions can be unambiguously synergistic or antagonistic, but neuromodulation often entails balanced adjustment of nonlinear membrane and synaptic properties by targeting ion channel and synaptic dynamics rather than just excitability or synaptic strength. In addition, neuromodulators can exert effects at multiple timescales, from short-term adjustments of neuron and synapse function to persistent long-term regulation. This short review summarizes some highlights of the diverse actions of neuromodulators on ion channel and synaptic properties.
Topics: Animals; Humans; Nerve Net; Neurons; Neurotransmitter Agents; Synapses; Synaptic Transmission
PubMed: 24907657
DOI: 10.1016/j.conb.2014.05.003 -
Anatomical Science International Jun 2021Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most... (Review)
Review
Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most excitatory synapses of pyramidal neurons are formed on spines, which are tiny protrusions extending from the dendritic shaft. The spine contains specialized molecular machinery that regulates synaptic transmission and plasticity. Spine size correlates with the efficacy of synaptic transmission, and spine morphology affects signal transduction at the post-synaptic compartment. Plasticity-related changes in the structural and molecular organization of spine synapses are thought to underlie the cellular basis of learning and memory. Recent advances in super-resolution microscopy have revealed the molecular mechanisms of the nanoscale synaptic structures regulating synaptic transmission and plasticity in living neurons, which are difficult to investigate using electron microscopy alone. In this review, we summarize recent advances in super-resolution imaging of spine synapses and discuss the implications of nanoscale structures in the regulation of synaptic function, learning, and memory.
Topics: Animals; Dendritic Spines; Humans; Microscopy; Neuronal Plasticity; Neurons; Prosencephalon; Synapses; Synaptic Transmission
PubMed: 33459976
DOI: 10.1007/s12565-021-00603-0 -
Advances in Experimental Medicine and... 2016Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the... (Review)
Review
Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus.
Topics: Animals; Enteric Nervous System; Humans; Neurobiology; Synaptic Transmission
PubMed: 27379645
DOI: 10.1007/978-3-319-27592-5_17 -
Neuron May 2016Regulation of neurotransmitter receptor localization is critical for synaptic function and plasticity. In this issue of Neuron, Matsuda and colleagues (Matsuda et al.,... (Review)
Review
Regulation of neurotransmitter receptor localization is critical for synaptic function and plasticity. In this issue of Neuron, Matsuda and colleagues (Matsuda et al., 2016) uncover a transsynaptic complex consisting of neurexin-3, C1q-like proteins, and kainate receptors that drives glutamate receptor clustering at hippocampal synapses.
Topics: Animals; Excitatory Postsynaptic Potentials; Hippocampus; Humans; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 27196968
DOI: 10.1016/j.neuron.2016.05.007