1 / 63

Neuroscience

Neuroscience. Crystal Sigulinsky Neuroscience Graduate Program University of Utah crystal.cornett@utah.edu. Housekeeping Notes. Posting lectures online Writing Assignment Listed as #4 due Monday July 7 th July 6 th = Monday Office hours

Pat_Xavi
Download Presentation

Neuroscience

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Neuroscience Crystal Sigulinsky Neuroscience Graduate Program University of Utah crystal.cornett@utah.edu

  2. Housekeeping Notes • Posting lectures online • Writing Assignment • Listed as #4 due Monday July 7th • July 6th = Monday • Office hours • Friday, July 3rd, 5-6 pm, Moran Eye Center 3rd floor lobby • By appointment • Test • Friday, July 10th

  3. Physics in Visual Processes • Imaging in the eye • Optics • Absorption of light in the eye • Quantum mechanics • Nerve conduction • Visual Information Processing http://en.wikipedia.org/wiki/File:Gray722.png Gray's Anatomy of the Human Body, 1918

  4. Neuroscience • Scientific study of the nervous system • Highly interdisciplinary • Structure/function • Development/Evolution • Genetics • Biochemistry • Physics • Physiology • Pathology • Informatics/Computational http://en.wikipedia.org/wiki/Image:Sagittal_brain_MRI.JPG

  5. Objectives • Basic Anatomy of the Nervous System • Organization • Cells • Neurons • Structure • Mechanism of function • Modeling neurons • Neurodegenerative Diseases

  6. Nervous System • Multicellular organisms • Specialized cells • Complex information processing system • Innervates the entire body • Substrate for thought and function • Gathers information • External = Organism’s environment • Internal = Organism’s self • Processing • Response initiated • Perception • Muscle activity • Hormonal change

  7. Nervous System Anatomy: Gross Organization • Central Nervous System (CNS) • Brain • Spinal cord • Peripheral Nervous System (PNS) • Cranial and spinal nerves • Motor and sensory • Somatic NS • “Conscious control” • Autonomic NS • “Unconscious control” http://en.wikipedia.org/wiki/File:Nervous_system_diagram.png

  8. http://en.wikipedia.org/wiki/File:NSdiagram.png

  9. Nervous System Anatomy: Cells • Neurons (Nerve Cells) • Receive, process, and transmit information • Glia • Not specialized for information transfer • Primarily a supportive role for neurons

  10. Neurons Wei-Chung Allen Lee, Hayden Huang, Guoping Feng, Joshua R. Sanes, Emery N. Brown, Peter T. So, Elly Nedivi http://en.wikipedia.org/wiki/File:Smi32neuron.jpg http://en.wikipedia.org/wiki/Neuron

  11. Neurons • Neuron Doctrine • Santiago Ramon y Cajal, 1891 • The neuron is the functional unit of the nervous system • Specialized cell type • Very diverse in structure and function • Sensory, interneurons, and motor neurons Above: sparrow optic tectum Below: chick cerebellum http://en.wikipedia.org/wiki/Santiago_Ram%C3%B3n_y_Cajal

  12. Neuron: Structure Axon Axon hillock http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png

  13. Neuron: Structure/Function • Specially designed to receive, process, and transmit information • Dendrites: receive information from other neurons • Soma: “cell body,” contains necessary cellular machinery, signals integrated prior to axon hillock • Axon: transmits information to other cells (neurons, muscles, glands) • Polarized • Information travels in one direction • Dendrite → soma → axon Axon hillock http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png

  14. Glia • Major cell type of the Nervous System • ~10X as many glia as neurons • Not designed to receive and transmit information • Do influence information transfer by neurons • Glia = “Glue” (Greek) • Support neurons • Maintain a proper environment • Supply oxygen and nutrients • Clear debris and pathogens • Guide development • Modulate neurotransmission • Myelination

  15. Glia: Types • Macroglia • Astrocytes • Regulate microenvironment in CNS • Form Blood-Brain Barrier • Oligodendrocytes • Myelinate axons of the CNS • Schwann Cells • Myelinate axons of the PNS • Microglia • Clean up in the CNS http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png

  16. How do neurons work? • Function • Receive, process, and transmit information • Signals • Chemical • Electrical

  17. Bioelectricity • Electric current generated by living tissue • History Electric Rays (Torpedos) Electric Eels http://en.wikipedia.org/wiki/File:Torpedo_fuscomaculata2.jpg http://en.wikipedia.org/wiki/File:Electric-eel2.jpg

  18. Bioelectricity • Electric current generated by living tissue • History • Electric fish • "Animal electricity” • Luigi Galvani, 1786 • Role in muscle activity • Inspiration behind Volta’s development of the battery http://en.wikipedia.org/wiki/File:Galvani-frog-legs.PNG

  19. Bioelectricity • Electric current generated by living tissues • Motion of positive and negative ions in the body • Essential for cellular and bodily functions • Storage of metabolic energy • Performing work • Cell-cell signaling • Sensation • Muscle control • Hormonal balance • Cognition • Important Diagnostic Tool

  20. How do neurons work? • Function • Receive, process, and transmit information • Unidirectional information transfer • Signals • Chemical • Electrical • What is the electrical state of a cell?

  21. Membrane Potential • Difference in electrical potential across cell membrane • Generated in all cells • Produced by separation of charges across cell membrane • Ion solutions • Extracellular fluid • Cytoplasm • Cell membrane • Impermeable barrier • Ion channels • Permit passage of ions through cell membrane • Passive (leaky channels) = with gradient • Active = against gradient • Resting membrane potential • KCl Simple Model

  22. Driving Forces • Chemical driving force • Fick’s First Law of Diffusion • Species move from region of high concentration to low concentration until equilibrium • Passive mechanism • Electrical driving force • Charged species in an electric field move according to charge • Passive mechanism

  23. Nernst Equation • Calculates the equilibrium potential for each ion • R = gas constant, T = temperature, F = Faraday constant, z = charge of the ion • Assumptions: • Membrane is permeable to ion • Ion is present on both sides of membrane

  24. [Na+] = 15 mM [K+] = 150 mM [Cl-] = 9 mM [A-] = 156 mM [Na+] = 145 mM [K+] = 5 mM [A+] = 5 mM [Cl-] = 125 mM [A-] = 30 mM Ion Distributions Cell Membrane Cytoplasm Extracellular Fluid - - - - - - - - + + + + + + + +

  25. Driving Forces • Chemical driving force • Fick’s First Law of Diffusion • Species move from region of high concentration to low concentration until equilibrium • Passive mechanism • Electrical driving force • Charged species in an electric field move according to charge • Passive mechanism • Na+/K+ pump • Active transport pump • 3Na+ out of cell • 2 K+ into cell • Aids to set up and maintain initial concentration gradients

  26. Resting Membrane Potential • Actually 4 ions (K+, Na+,Cl-, Ca2+) that strongly influence potential • Goldman-Hodgkin-Katz Equation • Takes into account all ionic species and calculates the membrane potential • P = permeability • Proportional to number of ion channels allowing passage of the ion • Not specific to the resting membrane potential • Can replace p with conductance (G) and [ion]in/[ion]out with Eion • Greater the membrane permeability = greater influence on membrane potential • Permeability: PK: PNa: PCl = 1 : 0.04 : 0.45 • Cl- typically not pumped, so at equilibrium • K+ dominates because greatest conductance • Resting membrane potential usually very negative -70 mV

  27. Electric Signals • Deviation in the membrane potential of the cell • Depolarization • Reduction of charge separation across membrane • Less negative membrane potential • Hyperpolarization • Increase in charge separation across membrane • More negative membrane potential • Cause: Ion channels open/close • Large change in permeability of ions relative to each other • Negligible change in bulk ion concentrations! • Induce changes in net separation of charge across cell membrane • Goldman equation only applies to steady state

  28. Electric Signals • Initiated by discrete events • Sensory neurons • Examples: • Vision: photoreceptors - absorb light triggering a chemical signaling cascade that opens voltage-gated ion channels • Touch: mechanoreceptors - mechanical pressure or distortion opens stress-gated voltage channels • Neuron-neuron, neuron-muscle, neuron-gland • Chemical signals open ligand-gated ion channels at the Synapse

  29. Synapse • Functional connections between neurons • Mediates transfer of information • Allows for information processing • Axon terminal “talks to” dendrite of another neuron • Neurotransmitters activate ligand-gated ion channels http://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svg

  30. Electric Signals • Deviation in the membrane potential of the cell • Spread according to different mechanisms • Electrotonic conduction • Dendrites • Action Potential • Axons

  31. Neuron: Structure Axon Axon hillock http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png

  32. x = 0 Change in Potential Distance (x) Electrotonic Conduction • Passive spread of electrical potential • Induced point increase in ion concentration • Na+ channels opened • Na+ flows into cell • Membrane potential shifts toward Na+ equilibrium potential (positive) • Depolarization • Diffusion of ions • Chemical gradient • Charge (electrical) gradient • Potential dissipates as distance from source increases Na+

  33. Electrotonic Conduction • Potential dissipates as distance from source increases • “Graded Potentials” • Summation • Spatially • Multiple sources of ion flux at different locations • Temporally • Repeated instances of ion flux at same location • Allows for information processing

  34. Processing http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png • A single neuron receives inputs from many other neurons • Input locations • Dendrites – principle site • Soma – low occurance • Inputs converge as they travel through the neuron • Changes in membrane potential sum temporally and spatially

  35. Axon hillock Transmitting Information • Signal inputs do not always elicit an output signal • Change in membrane potential must exceed the threshold potential for an action potential to be produced • Mylenated axons • Axon hillock = trigger zone for axon potential • Unmyelenated axons • Action potentials can be triggered anywhere along axon http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png http://en.wikipedia.org/wiki/File:Action_potential_vert.png

  36. Action Potentials • “All-or-none” principle • Sufficient increase in membrane potential at the axon hillock opens voltage-gated Na+ channels • Na+ influx further increases membrane potential, opening more Na+ channels • Establishes a positive feedback loop • Ensures that all action potentials are the SAME size • Also, complete potential is regenerated each time, so does not fade out • Turned off by opening of voltage gated K+ channels http://en.wikipedia.org/wiki/File:Action_potential_vert.png Figure: Ion channel openings during action potential http://faculty.washington.edu/chudler/ap.html

  37. Action Potential Propagation • Velocity • Action potential in one region of axon provides depolarization current for adjacent region • Passive spread of depolarization is not instantaneous • Electrotonic conduction is rate-limiting factor • Unidirectional • Voltage gated channels take time to recover • Cannot reopen for a set amount of time, ensuring signal travels in one direction

  38. Transmitting Information The Synapse • Presynaptic action potential causes a change in membrane polarization at the axon terminals • Votage-modulated Ca2+ channels open • Neurotransmitter is released • Activates ligand-gated ion channels on dendrites of next cell http://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svg

  39. + + i Battery Resistor - + - + - + - + Capacitor Modeling Neurons • Neurons are electrically active • Model as an electrical circuit • Battery • Current (i) generator • Resistor • Capacitor

  40. Membranes as Capacitors • Capacitor • Two conductors separated by an insulator • Causes a separation of charge • Positive charges accumulate on one side and negative charges on the other • Plasma Membrane • Lipid bilayer = insulator • Separates electrolyte solutions = conductors http://en.wikipedia.org/wiki/File:NeuronCapacitanceRev.jpg

  41. Ionic Gradients as Batteries • Concentration of ions differ between inside the neuron and outside the neuron • Additionally, Na+/K+ pump keeps these ions out of equilibrium • Ion channels permeate the membrane • Selective for passage of certain ions • Vary in their permeability • Always open to some degree = “leaky” • Net Result: each ionic gradient acts as a battery • Battery • Source of electric potential • An electromotive force generated by differences in chemical potentials • Ionic battery • Voltage created is essentially the electrical potential needed (equal and opposite) to cancel the diffusion potential of the ions so equal number of ions enter and leave the neuron • Establish the resting membrane potential of the neuron

  42. Ion Channels as Resistors • Resistor • Device that impedes current flow • Generates resistance (R) • Ion channels vary in their permeability • “Leaky” • Always permeable to some degree • Permeability is proportional to conductivity • Conductance (g) = 1/R • Ion channels modeled as a battery plus a resistor • Leak channels • Linear conductance relationship, gL • Voltage-gated channels • Non-linear conductance relationship, gn(t,V)

  43. Neuron modeled as an Electrical Circuit Ion pump Created by Behrang Amini http://en.wikipedia.org/wiki/File:Hodgkin-Huxley.jpg

  44. Cable Equation • Describes the passive spread of voltage change in the membrane of dendrites and axons • Time constant (τ) • Capacitor takes time to rearrange charges • Length constant (λ) • Spread of voltage change inhibited by resistance of the cytoplasm (axial resistance) • Spread of voltage limited by membrane resistance (leak channels) http://en.wikipedia.org/wiki/File:NeuronResistanceCapacitanceRev.jpg

  45. Hodgkin-Huxley Model • Describes how action potentials in neurons are initiated and propagated Nrets at en.wikipedia http://en.wikipedia.org/wiki/File:MembraneCircuit.jpg

  46. Neuron Design Objectives • Maximize computing power • Increase neuron density • Requires neurons be small • Maximize response ability • Minimize response time to changes in environment • Requires fast conduction velocities

  47. Passive Electrical Properties • Limitations to the design objectives • Action potential generated in one segment provides depolarization current for adjacent segment • Membrane is a capacitor • Takes time to move charges • Rate of passive spread varies inversely with the product of axial resistance and capacitance • = raCm

  48. Passive Electrical Properties • Membrane Capacitance (C) • Limits the conduction velocity • ΔV = Ic x Δt / C, where Ic = current flow across capacitor, t = time, and C = capacitance • Takes time to unload the charge on a capacitor when changing potential. • Function of surface area of plates (A), distance between plates (d) and insulator properties (ε) • Lipid bilayer = great insulator properties and very thin = high capacitance • Smaller neuron = smaller area = shorter time to change membrane potential = faster conduction velocity

  49. Passive Electrical Properties • Axial resistance (ra) • Limits conduction velocity • Ohm’s Law: ΔV = I x ra • ra = ρ/πa2 • ρ = resistance of cytoplasm, a = cross-sectional area of process • Increases with decreasing axonal radius • Larger axon = smaller axial resistance = larger current flow = shorter time to discharge the capacitor around axon = faster conduction velocity

  50. Passive Electrical Properties • Input resistance (Rin) • Limits the change in membrane potential • Ohm’s Law: ΔV = I x Rin • Rin = Rm/4πa2 • Rm = specific membrane resistance • Function of ion channel density and their conductance • Rin = function of Rm and cross sectional area of process • Smaller axon = fewer channels and smaller area = greater resistance = smaller current for a given membrane potential = longer time to discharge capacitor = slower conduction velocities

More Related