Physiology of Synapses and Receptors
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Nervous Tissue
Nervous Tissue Prof.Prof. ZhouZhou LiLi Dept.Dept. ofof HistologyHistology andand EmbryologyEmbryology Organization:Organization: neuronsneurons (nerve(nerve cells)cells) neuroglialneuroglial cellscells Function:Function: Ⅰ Neurons 1.1. structurestructure ofof neuronneuron somasoma neuriteneurite a.a. dendritedendrite b.b. axonaxon 1.11.1 somasoma (1)(1) nucleusnucleus LocatedLocated inin thethe centercenter ofof soma,soma, largelarge andand palepale--stainingstaining nucleusnucleus ProminentProminent nucleolusnucleolus (2)(2) cytoplasmcytoplasm (perikaryon)(perikaryon) a.a. NisslNissl bodybody b.b. neurofibrilneurofibril NisslNissl’’ss bodiesbodies LM:LM: basophilicbasophilic massmass oror granulesgranules Nissl’s Body (TEM) EMEM:: RERRER,, freefree RbRb FunctionFunction:: producingproducing thethe proteinprotein ofof neuronneuron structurestructure andand enzymeenzyme producingproducing thethe neurotransmitterneurotransmitter NeurofibrilNeurofibril thethe structurestructure LM:LM: EM:EM: NeurofilamentNeurofilament micmicrotubulerotubule FunctionFunction cytoskeleton,cytoskeleton, toto participateparticipate inin substancesubstance transporttransport LipofuscinLipofuscin (3)(3) CellCell membranemembrane excitableexcitable membranemembrane ,, receivingreceiving stimutation,stimutation, fromingfroming andand conductingconducting nervenerve impulesimpules neurite: 1.2 Dendrite dendritic spine spine apparatus Function: 1.3 Axon axon hillock, axon terminal, axolemma Axoplasm: microfilament, microtubules, neurofilament, mitochondria, -
Protein Scaffolds in the Coupling of Synaptic Exocytosis and Endocytosis
REVIEWS Protein scaffolds in the coupling of synaptic exocytosis and endocytosis Volker Haucke*§, Erwin Neher‡ and Stephan J. Sigrist§|| Abstract | Mechanisms that ensure robust long-term performance of synaptic transmission over a wide range of activity are crucial for the integrity of neuronal networks, for processing sensory information and for the ability to learn and store memories. Recent experiments have revealed that such robust performance requires a tight coupling between exocytic vesicle fusion at defined release sites and endocytic retrieval of synaptic vesicle membranes. Distinct presynaptic scaffolding proteins are essential for fulfilling this requirement, providing either ultrastructural coordination or acting as signalling hubs. Active zone Communication between nerve cells largely occurs at restore functional synaptic vesicle pools for reuse and to 6–8 (Often abbreviated to AZ.) An chemical synapses — specialized sites of cell–cell con- ensure long-term functionality of the synapse (FIG. 1). area in the presynaptic tact where electrical signals trigger the exocytic release Depending on the type of synapse and the stimulation fre- compartment that is specialized of neurotransmitter, which in turn activates postsynaptic quency, several modes of endocytosis with different time for rapid exocytosis and contains multidomain proteins receptor channels. The efficacy with which such chemi- constants — for example, fast and slow endocytosis — 7,9,10 acting as scaffolds in the cal signals are transmitted is crucial for the functioning seem to operate . Clathrin-mediated endocytosis organization of release sites. of the nervous system. Modulation of neurotransmission arguably represents the main pathway of synaptic vesicle 6,8,11 Periactive zone enables nerve cells to respond to a vast range of stimu- endocytosis , although other modes — for example, An array of endocytic proteins lus patterns. -
Presynaptic Modulation of Synaptic Transmission and Plasticity by Brain-Derived Neurotrophic Factor in the Developing Hippocampus
The Journal of Neuroscience, September 1, 1998, 18(17):6830–6839 Presynaptic Modulation of Synaptic Transmission and Plasticity by Brain-Derived Neurotrophic Factor in the Developing Hippocampus Wolfram Gottschalk,1 Lucas D. Pozzo-Miller,2 Alexander Figurov,1 and Bai Lu1 1Unit on Synapse Development and Plasticity, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, and 2Laboratory of Neurobiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892 In addition to the regulation of neuronal survival and differenti- interpulse intervals #20 msec. Changes in the extracellular ation, neurotrophins may play a role in synapse development calcium concentration altered the magnitude of the BDNF effect and plasticity. Application of brain-derived neurotrophic factor on PPF and synaptic responses to HFS, suggesting that BDNF (BDNF) promotes long-term potentiation (LTP) in CA1 synapses regulates neurotransmitter release. When the desensitization of of neonatal hippocampus, which otherwise exhibit only short- glutamate receptors was blocked by cyclothiazide or anirac- term potentiation. This is attributable, at least in part, to an etam, the BDNF potentiation of the synaptic responses to HFS attenuation of the synaptic fatigue induced by high-frequency was unaltered. Taken together, these results suggest that BDNF stimulation (HFS). However, the prevention of synaptic fatigue acts presynaptically. When two pathways in the same slice by BDNF could be mediated by an attenuation of synaptic were monitored simultaneously, BDNF treatment potentiated vesicle depletion from presynaptic terminals and/or a reduction the tetanized pathway without affecting the synaptic efficacy of of the desensitization of postsynaptic receptors. Here we pro- the untetanized pathway. -
Absence of S100A4 in the Mouse Lens Induces an Aberrant Retina-Specific Differentiation Program and Cataract
www.nature.com/scientificreports OPEN Absence of S100A4 in the mouse lens induces an aberrant retina‑specifc diferentiation program and cataract Rupalatha Maddala1*, Junyuan Gao2, Richard T. Mathias2, Tylor R. Lewis1, Vadim Y. Arshavsky1,3, Adriana Levine4, Jonathan M. Backer4,5, Anne R. Bresnick4 & Ponugoti V. Rao1,3* S100A4, a member of the S100 family of multifunctional calcium‑binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in diferentiating fber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late‑onset cortical cataracts. Transcriptome profling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor‑ and Müller glia‑specifc genes, as well as the olfactory sensory neuron‑specifc gene, S100A5. This aberrant transcriptional profle is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of diferentially expressed genes in S100A4 (−/−) lenses identifed Crx and Nrl transcription factors as the most signifcant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high‑density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this fnding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, -
Electrical Synapses and Their Functional Interactions with Chemical Synapses
REVIEWS Electrical synapses and their functional interactions with chemical synapses Alberto E. Pereda Abstract | Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function. Communication between neurons is required for Electrical and chemical synapses are now known to brain function, and the quality of such communica- coexist in most organisms and brain structures, but details tion enables hardwired neural networks to act in a of the properties and distribution of these two modalities of dynamic fashion. Functional interactions between transmission are still emerging. Most research efforts neurons occur at anatomically identifiable cellular have focused on exploring the mechanisms of chemi- regions called synapses. Although the nature of synaptic cal transmission, and considerably less is known transmission has been an area of enormous controversy about those underlying electrical transmission. It was (BOX 1), two main modalities of synaptic transmission — thought that electrical synapses were more abundant namely, chemical and electrical — are now recognized. At in invertebrates and cold-blooded vertebrates than chemical synapses, information is transferred through in mammals. -
The Presynaptic Scaffold Protein Bassoon in Forebrain Excitatory Neurons Mediates Hippocampal Circuit Maturation: Potential Involvement of Trkb Signalling
International Journal of Molecular Sciences Article The Presynaptic Scaffold Protein Bassoon in Forebrain Excitatory Neurons Mediates Hippocampal Circuit Maturation: Potential Involvement of TrkB Signalling Anil Annamneedi 1,2,3,* , Miguel del Angel 1, Eckart D. Gundelfinger 2,3,4, Oliver Stork 1,2 and Gürsel Çalı¸skan 1,2,* 1 Institute of Biology, Otto-Von-Guericke University, 39120 Magdeburg, Germany; [email protected] (M.d.A.); [email protected] (O.S.) 2 Center for Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany; [email protected] 3 Leibniz Institute for Neurobiology (LIN), RG Neuroplasticity, 39118 Magdeburg, Germany 4 Institute of Pharmacology & Toxicology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany * Correspondence: [email protected] (A.A.); [email protected] (G.Ç.) Abstract: A presynaptic active zone organizer protein Bassoon orchestrates numerous important func- tions at the presynaptic active zone. We previously showed that the absence of Bassoon exclusively in forebrain glutamatergic presynapses (BsnEmx1cKO) in mice leads to developmental disturbances in dentate gyrus (DG) affecting synaptic excitability, morphology, neurogenesis and related behaviour during adulthood. Here, we demonstrate that hyperexcitability of the medial perforant path-to-DG (MPP-DG) pathway in BsnEmx1cKO mice emerges during adolescence and is sustained during adult- Citation: Annamneedi, A.; del hood. We further provide evidence for a potential involvement of tropomyosin-related kinase B Angel, M.; Gundelfinger, E.D.; Stork, (TrkB), the high-affinity receptor for brain-derived neurotrophic factor (BDNF), mediated signalling. O.; Çalı¸skan,G. The Presynaptic We detect elevated TrkB protein levels in the dorsal DG of adult mice (~3–5 months-old) but not in Scaffold Protein Bassoon in Forebrain Excitatory Neurons Mediates adolescent (~4–5 weeks-old) mice. -
11 Introduction to the Nervous System and Nervous Tissue
11 Introduction to the Nervous System and Nervous Tissue ou can’t turn on the television or radio, much less go online, without seeing some- 11.1 Overview of the Nervous thing to remind you of the nervous system. From advertisements for medications System 381 Yto treat depression and other psychiatric conditions to stories about celebrities and 11.2 Nervous Tissue 384 their battles with illegal drugs, information about the nervous system is everywhere in 11.3 Electrophysiology our popular culture. And there is good reason for this—the nervous system controls our of Neurons 393 perception and experience of the world. In addition, it directs voluntary movement, and 11.4 Neuronal Synapses 406 is the seat of our consciousness, personality, and learning and memory. Along with the 11.5 Neurotransmitters 413 endocrine system, the nervous system regulates many aspects of homeostasis, including 11.6 Functional Groups respiratory rate, blood pressure, body temperature, the sleep/wake cycle, and blood pH. of Neurons 417 In this chapter we introduce the multitasking nervous system and its basic functions and divisions. We then examine the structure and physiology of the main tissue of the nervous system: nervous tissue. As you read, notice that many of the same principles you discovered in the muscle tissue chapter (see Chapter 10) apply here as well. MODULE 11.1 Overview of the Nervous System Learning Outcomes 1. Describe the major functions of the nervous system. 2. Describe the structures and basic functions of each organ of the central and peripheral nervous systems. 3. Explain the major differences between the two functional divisions of the peripheral nervous system. -
Neuronal Signaling Neuroscience Fundamentals > the Nerve Cell > the Nerve Cell
Neuronal Signaling Neuroscience Fundamentals > The Nerve Cell > The Nerve Cell NEURONAL SIGNALING SUMMARY ACTION POTENTIALS See: Action Potentials Key Features • All-or-nothing events • Self-propagating • Conduction speed determined by axon diameter (thicker means faster) and amount of myelination (more myelin means faster transmission). CHEMICAL SYNAPSE Steps of Chemical Synapsis 1) The action potential travels down axon of presynaptic neuron. 2) Vesicle fuses with plasma membrane and releases neurotransmitter into the synaptic cleft. 3) Neurotransmitters bind to ligand-gated ion channels, opening them. 4) Ions entering through the open channels cause a depolarization of the membrane, opening voltage-gated ion channels. 5) Ions pass through these voltage-gated ion channels, causing further depolarization of the membrane. 6) This depolarization (action potential) travels along the membrane as more voltage-gated ion channels are opened. ELECTRICAL SYNAPSE • Cytoplasms of adjacent neurons are connected, allowing ions (and action potentials) to travel directly to the next cell. NEURONAL CODING OF STIMULUS STRENGTH Action Potential Frequency • Stimulus strength is based on frequency of action potentials. Action Potential Strength • Strong stimuli can produce another action potential during the relative refractory period. 1 / 7 ABSOLUTE REFRACTORY PERIOD No further action potentials • Voltage-gated sodium channels are open or inactivated so another stimulus, no matter its strength, CANNOT elicit another action potential. RELATIVE REFRACTORY -
Synapse Transmission
Synapse Transmission There are two types of synapses found in your body: electrical and chemical. Electrical synapses allow the direct passage of ions and signaling molecules from cell to cell. In contrast, chemical synapses do not pass the signal directly from the presynaptic cell to the postsynaptic cell. In a chemical synapse, an action potential in the presynaptic neuron leads to the release of a chemical messenger called aneurotransmitter. The neurotransmitter then diffuses across the synapse and binds to receptors on the postsynaptic cell. Binding of the neurotransmitter leads to the production of an electrical signal in the postsynaptic cell. Why does the body have two types of synapses? Each type of synapse has functional advantages and disadvantages. An electrical synapse passes the signal very quickly, which allows groups of cells to act in unison. A chemical synapse takes much longer to transmit the signal from one cell to the next; however, chemical synapses allow neurons to integrate information from multiple presynaptic neurons, determining whether or not the postsynaptic cell will continue to propagate the signal. Neurons respond differently based on information transmitted by multiple chemical synapses. Let’s take a closer look at the structure and function of each type of synapse. Electrical synapses transmit action potentials via the direct flow of electrical current at gap junctions. Gap junctions are formed when two adjacent cells have transmembrane pores that align. The membranes of the two cells are linked together and the aligned pores form a passage between the cells. Consequently, several types of molecules and ions are allowed to pass between the cells. -
Synaptic Transmission Dr
Synaptic Transmission Dr. Simge Aykan Department of Physiology Synaptic Transmission • Biological process by which a neuron communicates with a target cell across a synapse • Synapse is an anatomically specialized junction between two neurons, at which the electrical activity in a presynaptic neuron influences the electrical activity of a postsynaptic neuron • Synapse can be between a neuron and a • Neuron • Muscle • Gland cell Synaptic Transmission • The average neuron forms several thousand synaptic connections and receives a similar number • The Purkinje cell of the cerebellum receives up to 100,000 synaptic inputs • 1011 neurons, 1014 (100 trillion!) synapses Synaptic Transmission • Electrical synapse transmission: transfer of electrical signals through gap junctions • Chemical synaptic transmission: release of a neurotransmitter from the pre-synaptic neuron, and neurotransmitter binding to specific post-synaptic receptors Electrical Synapses • Connection through gap junctions • Narrow gap between membranes (3 nm) • Connexin connexon gap junction • Direct ion passage from one neuron to another • Big enough for many small organic molecules to pass through (1-2 nm) • Mostly between dendrites Electrical Synapses • Electrical postsynaptic potential (PSP) induced by ionic current flow (1 mV or less) Electrical Synapses • Advantages • Extremely rapid • Orchestrating the actions of large groups of neurons • Can transmit metabolic signals between cells • Less common in vertebrate nervous system • Require a large area of contact; restricting -
SHORT-TERM SYNAPTIC PLASTICITY Robert S. Zucker Wade G. Regehr
23 Jan 2002 14:1 AR AR148-13.tex AR148-13.SGM LaTeX2e(2001/05/10) P1: GJC 10.1146/annurev.physiol.64.092501.114547 Annu. Rev. Physiol. 2002. 64:355–405 DOI: 10.1146/annurev.physiol.64.092501.114547 Copyright c 2002 by Annual Reviews. All rights reserved SHORT-TERM SYNAPTIC PLASTICITY Robert S. Zucker Department of Molecular and Cell Biology, University of California, Berkeley, California 94720; e-mail: [email protected] Wade G. Regehr Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115; e-mail: [email protected] Key Words synapse, facilitation, post-tetanic potentiation, depression, augmentation, calcium ■ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemi- cal synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that re- sult from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a resid- 2 ual elevation in presynaptic [Ca +]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other 2 2 factors such as alterations in presynaptic Ca + influx or postsynaptic levels of [Ca +]i. -
Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner
12214 • The Journal of Neuroscience, August 29, 2012 • 32(35):12214–12227 Cellular/Molecular Synapsins Contribute to the Dynamic Spatial Organization of Synaptic Vesicles in an Activity-Dependent Manner Eugenio F. Fornasiero,1 Andrea Raimondi,2 Fabrizia C. Guarnieri,1 Marta Orlando,2 Riccardo Fesce,1,3 Fabio Benfenati,2,4 and Flavia Valtorta1 1San Raffaele Scientific Institute and Vita-Salute University, I-20132 Milan, Italy, 2Department of Neuroscience and Brain Technologies, Italian Institute of Technology, I-16163 Genoa, Italy, 3Neuroscience Center, Insubria University, I-21100 Varese, Italy, and 4Department of Experimental Medicine, University of Genoa and National Institute of Neuroscience, I-16132 Genoa, Italy The precise subcellular organization of synaptic vesicles (SVs) at presynaptic sites allows for rapid and spatially restricted exocytotic release of neurotransmitter. The synapsins (Syns) are a family of presynaptic proteins that control the availability of SVs for exocytosis by reversibly tethering them to each other and to the actin cytoskeleton in a phosphorylation-dependent manner. Syn ablation leads to reductioninthedensityofSVproteinsinnerveterminalsandincreasedsynapticfatigueunderhigh-frequencystimulation,accompanied by the development of an epileptic phenotype. We analyzed cultured neurons from wild-type and Syn I,II,IIIϪ/Ϫ triple knock-out (TKO) miceandfoundthatSVswereseverelydispersedintheabsenceofSyns.VesicledispersiondidnotaffectthereadilyreleasablepoolofSVs, whereas the total number of SVs was considerably reduced