Lect 1-09-CNS

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    LECTURE 1 OUTLINE

    CYTOLOGY OF NEURONS

    CLASSIFICATION OF NEURONS

    SYNAPSES

    MYELINATION

    NEURONAL CYTOSKELETON

    SYNTHESIS AND TRAFFICKING OF NEURONAL PROTEINS

    NEURONAL EXTENSION AND MIGRATION

    NEURONAL CELL BIOLOGY

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    Medical Physiology, Boron and Boulpaep, p. 259

    Morphology of a Typical Neuron

    Dendrites

    Dendritic Spines

    Soma (cell body)

    Axon

    Axon hillock

    Initial segment

    Myelin sheath

    Node of Ranvier

    Presynaptic terminal

    Synaptic cleft

    CYTOLOGY OF NEURONS

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    CLASSIFICATION OF NEURONS

    Basis for classification

    Axonal projection

    Dendritic pattern

    Number of processes

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    Goes to distant

    CNS area

    Stays in local

    CNS areaIntrinsic neuron or

    Interneuron

    Retinal bipolar cell

    Cortical inhibitory neuron

    Basis for

    classificationFunctional Implication Structure and Examples

    Axonal projection

    Affects different CNS

    areas

    Affects only nearby

    neurons

    Projection neuron or

    Principal neuron

    Dorsal root ganglion cell

    Cortical motor neuron

    Medical Physiology, Boron and Boulpaep, p.263

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    Basis for

    classificationFunctional Implication Structure and Examples

    Dendritic pattern

    Pyramid-

    shaped spread

    of dendrites

    Radial-shapedspread of

    dendrites

    Large area for receiving

    synaptic input; determines

    the pattern of incoming

    axons that can interact with

    the cell -Pyramid shaped

    Large area for receiving

    synaptic input; determines

    the pattern of incoming

    axons that can interact with

    the cell-Star-shaped

    Hippocampal pyramidalneuron

    Cortical stellate cell

    Medical Physiology, Boron and Boulpaep, p.263

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    Basis for

    classificationFunctional Implication Structure and Examples

    Medical Physiology, Boron and Boulpaep, p.263

    Number of

    processes

    One process

    exits the cell

    body

    Two processes

    exit the cell

    body

    Many

    processes exit

    the cell body

    Small area for receiving

    synaptic input; highly

    specialized function

    Small area for receiving

    synaptic input; highly

    specialized function

    Large area for receiving

    synaptic input; determines

    the pattern of incoming

    axons that can interact with

    the cell

    Unipolar neuron

    Dorsal root ganglion cell

    Bipolar neuron

    Retinal bipolar cell

    Multipolar neuron

    Spinal motor neuron

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    Types of Synapses

    Axospinous

    Axodendritic

    Axosomatic

    Axoaxonic

    SYNAPSES

    Medical Physiology, Boron and Boulpaep, p. 300

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    Typical anterior spinal motor neuron

    A neuron receives multiple inputs and must

    integrate the information

    Textbook of Medical Physiology, 10th Ed. Guyton and Hall p,516

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    MYELINATION

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.81

    1. Peripheral Nervous System

    Sensory or motor neuron

    Schwann cells

    Nodes of Ranvier

    Myelin composed of proteolipid, sphingomyelin, and myelin specific

    proteins

    Expression of mylein genes regulated by contact between axon and

    Schwann cell

    Mesaxon

    Mature myelin sheath

    SC

    Axon

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    2. Central Nervous System

    Oligodendrocyte (glial cell)

    A single oligodendrocyte typically ensheaths several axon processes

    Expression of myelin genes appears to depend on astrocytes.

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.81

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    NEURONAL CYTOSKELETON

    Neuronal cytoskeleton is the major intrinsic determinant of the

    shape of a neuron and is responsible for the asymmetric

    distribution of organelles within the cytoplasm.

    1. Microtubules

    2. Neurofilaments

    3. Microfilaments

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    Characteristics of Microtubules

    Extend full length

    Diameter 25-28 nm

    a- and - tubulinTubulin is GTPase

    Involved in transport of organelles

    Stabilized by microtubule associated

    proteins (MAPs)

    1. Microtubules

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.71

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    2. Neurofilaments

    Cytokeratin

    Most abundant10 nm diameter

    Polymerized

    Important in neuronal cell structure

    Characteristics of Neurofilaments

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.71

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    3. Microfilaments

    Characteristics of Microfilaments

    3-5 nm diameter

    and g actinInvolved in motility of growth cones and

    formation of pre- and post-synapticmorphologic specializations

    Dynamic changes in polymerization and

    depolymerization

    Often found in cell periphery under

    plasmalemma

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.71

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    SYNTHESIS AND TRAFFICKING OF NEURONAL PROTEINS

    Proteins are synthesized in the cell body, but must be transported to

    the axons and terminalsPrinciples of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.93

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    Ribosomal RNA is found in the cell body and

    dendrites, but not in the axon

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.90

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    Axoplasmic transport

    Medical Physiology, Boron and Boulpaep, p. 262

    The primary site of secretion,

    the axon terminal, is

    considerably distant from the

    cell body and dendrites where

    secretory proteins are

    synthesized

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    Medical Physiology, Boron and Boulpaep, p. 262

    Movement of membranous organelles

    Anterograde transport

    Kinesin or kinesin-related proteins

    Retrograde transport

    Dynein

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    Globular heads that bind microtubules

    Fan-shaped tail that binds the organelle

    Kinesin is a ATPase

    Hinge region allows walking along the microtubules

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.101

    Model for how kinesin may move organelles along microtubules

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    Fast anterograde transport

    Rate is 410 mm/day

    Saltatory movement along microtubules

    Disrupted by colchicine and vinblastine

    Motor molecule is kinesin

    ATP-dependent

    Not effected by protein synthesis inhibitors (after incorporation)

    Not dependent on the cell body

    Mitochondria and vesicles transported

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    Experiment establishing axoplasmic transport

    [3H] Leucine injected into the dorsal root ganglia in the lumbar region of

    the spinal cord and fragments of the sciatic nerve collected at specific

    times after injection. Experiment performed by Ochs and colleagues.

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.100

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    Fast retrograde transport

    Rate is 200-300 mm/day

    Saltatory movement along microtubules

    Motor molecule is dynein

    ATP-dependent

    Degraded vesicular membrane and absorbed exogenous material

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    Slow axoplasmic transport

    Anterograde direction only

    Rate is 0.2-5 mm/day

    Cytoskeletal proteins and cytoplasmic proteins such as

    intermediary metabolism enzymes

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    NEURONAL EXTENSION AND MIGRATION

    Principles of Neural Science, 4th Ed. Kandel, Schwartz and Jessell, p.1073

    Growth cone

    Filopodia extend

    Cell-matrix

    adhesion regulatedby integrins and their

    ligands-laminins

    Role for actin

    microfilaments to

    move filopodium

    forward (protrusion)

    Cell-cell adhesion

    controlled by

    cadherins, N-CAM

    and others

    Guidance -growthfactors from target

    cells

    Grow at rate of slow

    axoplasmic transport