Klyachko Lecture - TRANSMISSION OF INFORMATION IN THE...

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Unformatted text preview: TRANSMISSION OF INFORMATION IN THE NEURVOUS SYSTEM Vitaly Klyachko Introduction to BME Sept 13nd, 2010 Transmission of information Transmission Information must be transmitted within each neuron within – action potential conduction and between neurons and – synaptic transmission V.Gallese Neuron/Synapse Doctrine : Neuron/Synapse Milestones 1836: Purkinje stained and identified first neurons, suggested that nerve fibers originate from cell bodies 1839: Schwann proposed cell theory – all tissues consist of cells 1842: Helmholz experimentally showed that nerves originate from cell bodies 1873: Golgi invented silver nitrate staining method to visualize neurons 1888: Cajal used Golgi staining to identify individual neurons 1891: Walderyer proposed Neuron Doctrine Modern neuron staining Modern golgi staining, using fluorescent marker genetically encoded in the mice Tim Murphy lectures, UBC Information Information Transmission The Action The Potential Voltage-dependent sodium channels open. Na+ flow in. The membrane potential changes from -60mV to +40mV. Sodium channels rapidly close. Depolarization triggers opening of voltage-dependent potassium channels. K+ ions flow out, repolarizing the membrane. M. Bear. Neuroscience: Exploring the brain. 3d ed. Action Potential Conduction Action Propagation: Orthodromic: AP travels down axon to the synapse Antidromic (experimental): Backward propagation Conduction velocity: 10 m/s AP duration: 1-2 msec Why natural AP propagates only in one direction? M. Bear. Neuroscience: Exploring the brain. 3d ed. Conduction Velocity: Conduction The linear cable theory Assumptions: 1. Membrane parameters are linear: rm, ri, cm = constant, same for all parts of neuron and passive (voltage-independent) 2. Current flows along a single spatial dimension x. x 3. Extracellular resistance r0 = 0; ∂ 2Vm ∂Vm 2 + Vm =τm λ 2 ∂x ∂t λ= aR m 2 Ri τ m = Rm C m ii ri Cable equation Length constant Time constant im cm rm Parameters of the cable model λ is the length constant: λ determines the distance through which voltage spread along the cable. λ= aR m ~K a 2 Ri Potential spreads further in larger cables For a 1 μm diameter dendrite with Rm ≅ 104 Ω.cm2, λ ≅ 800 μm τm is the membrane time constant - determines how long it takes for membrane potential to change in response to an injected current. τ m = RmCm Conduction velocity of a passively Conduction propagating membrane potential Conduction velocity: How does the fiber size influence conduction velocity? a – axonal diameter For a 1 μm diameter axon with Rm ≅ 20kΩ.cm2, Θ ≅ 700 μm/msec Action Potential Conduction Passive conduction will ensure that adjacent Passive membrane depolarizes, so the AP “travels” down the axon. But transmission by continuous AP is relatively But slow and energy-consuming (Na+/K+ pump). slow energy A faster, more efficient mechanism has evolved: faster, saltatory conduction. saltatory Myelination provides saltatory conduction. Myelination V.Gallese Myelination Myelination Most mammalian axons are myelinated. Most myelinated The myelin sheath is provided by oligodendrocytes The oligodendrocytes (CNS) and Schwann cells (PNS). Schwann Myelin consists of multiple layers of membrane that Myelin prevent passage of ions across the axon’s membrane. V.Gallese Saltatory Conduction Saltatory Myelinated regions of axon are electrically insulated. Electrical Myelinated electrically charge moves along the axon rather than across the membrane. along Action potentials occur only at unmyelinated regions: nodes of Action unmyelinated nodes Ranvier. High Na+ channel concentration High Rm, no Im, only Ii Synaptic Transmission Synaptic Transmission of information Transmission Information must be transmitted: within each neuron – saltatory AP conduction within and between neurons – synaptic transmission and V.Gallese Why studying synaptic transmission is important? • Synapses are the computational units in the brain ~109 synapses / mm3 more synapses in the brain than stars in the universe • Synapses underlie all sensory experiences: vision, hearing, smell, taste and touch. • Synaptic deregulation causes many neurological disorders Alzheimer's, Parkinson’s, mental retardation • Synaptic transmission is essential for information processing, learning and memory Synapse hypothesis Synapse Charles Scott Sherrington Charles Discovered that neurotransmission has (synaptic) delay – nerve is not a continuous wire Invented term synapse Invented Described excitatory and inhibitory Described actions of neurotransmitters Only excitatory propagate, inhibitory Only modulates 1932 Nobel prize in Medicine 1932 Discovery of chemical Discovery neurotransmitter Otto Loewi Otto Showed that nerve stimulation liberates a diffusible transmitter. Perfusate from one stimulated Perfusate frog heart could be transferred to another and changes beat frequency. 1936 Nobel prize in Medicine 1936 Tim Murphy lectures, UBC Debate on synaptic transmission Debate chemical or electrical. Soup vs. Spark Debate: Soup Is synaptic transmission has a chemical nature (Soup) or is a direct transfer of electrical charge (Spark)? Pro-Chemical argument: Otto Loewi showed that acetylcholine Pro application mimics the effect of nerve stimulation Pro-Electrical argument: synaptic transmission in some cases Pro is too fast (submillisecond), can only be electrical. Eccles developed a model of electrical synapse for the Eccles neuromuscular junction explaining current flow at “the point of contact”. Subsequently both chemical and electrical transmission was Sub shown to exist. Chemical Electrical Nobel Prize 1970 Nobel Prize 1963 From Kristin Harris Lectures. http://synapses.mcg.edu/lab/harris/lectures.htm Electrical Synapses A hallmark of electrical transmission is a very short delay between presynaptic stimulus and postsynaptic response. M. Bear. Neuroscience: Exploring the brain. 3d ed. Electrical Synapses Electrical Gap junction: channel formed Gap by six connexins, 1-2nm pore Cells are “electrically coupled” Cells Flow of ions from cytoplasm to cytoplasm, bidirectionally Very fast transmission Very Synaptic delay: only ~0.2ms Good for rapid behaviours such as escape response. Allows synchronizations of neural Allows populations (networks). Used in inhibitory control, developing brain, heart. M. Bear. Neuroscience: Exploring the brain. 3d ed. , Fundamental Neuroscience Electrical Synapses Electrical Problems : No amplification mechanisms No Difficult to modulate properties Difficult Can't change sign Can't No real mechanisms for long-term changes No Hard to implement memory Cell size is important Cell Requires the presynaptic cell to be larger than the postsynaptic cell to inject considerable charge Chemical Synaptic Transmission A hallmark of chemical transmission is a delay between presynaptic stimulus and postsynaptic response. Tim Murphy lectures, UBC Chemical Synaptic Chemical Transmission Electron Micrograph of a synapse Active zone Postsynaptic neuron Presynaptic neuron vesicles Venkatesh N. Murthy lectures, Harvard Chemical Synaptic Chemical Transmission Synaptic vesicles, containing neurotransmitter, congregate at the Synaptic presynaptic active zone. The action potential causes voltage-gated calcium (Ca2+) channels to open; The Ca2+ ions flood in. Increase in Ca2+ concentration Increase causes vesicles to fuse with presynaptic membrane. Neurotransmitter is released Neurotransmitter into synaptic cleft and diffuses across to bind postsynaptic receptors. Activation of postsynaptic receptors cause influx of ions into postsynaptic Activation cell, altering membrane potential. Chemical Synaptic Chemical Transmission Multiple steps are required to release neurotransmitters Multiple and for them to act on postsynaptic receptors Synaptic delay: 0.2-2 msec. Unidirectional, localized action Unidirectional release machinery and receptors are localized at active zone/postsynaptic specializations Can change sign by release of inhibitory transmitter Can Easy to modulate: has many steps at presynaptic and at Easy the postsynaptic sites. Types of Synapses Types Types of Synapses By origin/target: By Axodendritic: Axon to dendrite Axosomatic: Axon to cell Body Axoaxonic: Axon to Axon Dendrodendritic: Dendrite to dendrite M. Bear. Neuroscience: Exploring the brain. 3d ed. Types of Synapses By architecture/ultrastructure: Type I, asymmetrical, (excitatory) Type II, symmetrical, (inhibitory) http://synapses.mcg.edu/atlas Types of Synapses Types By the number of release sites: Single release site (excitatory, CNS) Multiple release sites (Inhibitory, CNS Excitatory and inhibit., PNS) Fundamental. Neurosci 2nd ed. Neurotransmitters Neurotransmitters Three classes of neurotransmitters Three – Amino acids, amines, and peptides Many different neurotransmitters Many - Several neurotransmitters can be released from the same synapse. Example: GABA and Gly. Defining particular transmitter systems Defining – By the molecule, synthetic machinery, packaging, reuptake and degradation, etc. Acetylcholine (Ach) Acetylcholine – First identified neurotransmitter M. Bear. Neuroscience: Exploring the brain. 3d ed. Postsynaptic Postsynaptic Mechanisms Postsynaptic Receptors Postsynaptic Ionotropic: Ionotropic Transmitter-gated ion channels Metabotropic: Metabotropic G-protein-coupled receptors M. Bear. Neuroscience: Exploring the brain. 3d ed. Postsynaptic Receptors Postsynaptic Transmitter-Gated Channels Transmitter Fast synaptic transmission Fast Sensitive detectors of chemicals Sensitive and voltage Regulate flow of large currents Regulate Differentiate between similar Differentiate ions Basic structure: pentamer, Basic 4TM regions/subunit M. Bear. Neuroscience: Exploring the brain. 3d ed. Postsynaptic Receptors Postsynaptic Amino Acid-Gated Channels Glutamate-Gated: AMPA, NMDA, kainite. Glutamate Mediate Excitatory transm. GABA- and Glycine-Gated: GABA Mediate inhibitory transm. Bind ethanol, benzodiazepines, barbiturates Prime targets for drug development: anesthetics, anticonvulsant, depression, Alzheimer’s M. Bear. Neuroscience: Exploring the brain. 3d ed. Postsynaptic Receptors Postsynaptic G-Protein-Coupled Receptors and Effectors 3 basic operational steps: Binding of the neuroBinding transmitter to the receptor Activation of G-proteins Activation Activation of effector systems Activation The basic structure: The Single polypeptide with 7 membrane-spanning α-helices M. Bear. Neuroscience: Exploring the brain. 3d ed. Dendrites: Integration of Information Function of Dendrites Neurons have complex multiple compartment structure. Note the differences in voltage spread across the dendrites and how voltage spreads through the dendrtic tree with time. Membrane potential spread in a model dendritic tree of a Purkinje cell during dendritic AP Integration of Information Postsynaptic potentials: Postsynaptic Depending on the type of ion channel which opens, the postsynaptic cell membrane becomes either: Depolarized, more prone to firing an AP, excitatory, EPSP Hyperpolarized, less prone to firing an AP, inhibitory, IPSP M. Bear. Neuroscience: Exploring the brain. 3d ed. Integration of information Integration PSPs are small. An individual EPSP will not produce PSPs enough depolarization to trigger an action potential. IPSPs will counteract the effect of EPSPs at the same IPSPs neuron. Summation means the effect of many coincident Summation IPSPs and EPSPs at one neuron. If there is sufficient depolarization at the axon If axon hillock, an action potential will be triggered. axon hillock V.Gallese Integration of information Integration Synaptic Integration: Process by which multiple synaptic Synaptic potentials combine within one postsynaptic neuron M. Bear. Neuroscience: Exploring the brain. 3d ed. Integration of information EPSP Summation EPSP – Allows for neurons to perform sophisticated computations – Integration: EPSPs added together to produce significant postsynaptic depolarization – Spatial: EPSP generated simultaneously in different spaces – Temporal: EPSP generated at same synapse in rapid succession M. Bear. Neuroscience: Exploring the brain. 3d ed. ...
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This note was uploaded on 02/14/2012 for the course NUBITRY 3304 taught by Professor Various during the Spring '01 term at Albertus Magnus.

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