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Contents: The nervous system of the vertebrates 1. Main components 2. The mouse as a model 3. Brain and spinal cord 3.1 Evolution and development 3.2 Principles of organization 3.3 Blood and liquor system Literature: Dudel et al., Neurowissenschaft (Springer) Reichert, Neurobiologie (Thieme) Kandel et al., Principles of Neural Science (McGraw Hill) Kahle, Taschenatlas der Anatomie, Band 3: Nervensystem und Sinnesorgane (Thieme) Greenstein and Greenstein, Color Atlas of Neuroscience (Thieme) Development and anatomical organization of the nervous system II

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  • Contents:

    The nervous system of the vertebrates

    1. Main components

    2. The mouse as a model

    3. Brain and spinal cord

    3.1 Evolution and development

    3.2 Principles of organization

    3.3 Blood and liquor system

    Literature:

    Dudel et al., Neurowissenschaft (Springer)

    Reichert, Neurobiologie (Thieme)

    Kandel et al., Principles of Neural Science (McGraw Hill)

    Kahle, Taschenatlas der Anatomie, Band 3: Nervensystem und

    Sinnesorgane (Thieme)

    Greenstein and Greenstein, Color Atlas of Neuroscience (Thieme)

    Development and anatomical organization of the

    nervous system II

  • Increase in centralization and cephalization:

    In humans, the majority of the neurons are located in the brain and about

    99,999% of the nerve cells are interneurons

    The nervous system of the vertebrates

    Sensory

    InputMotor

    outputIntegration

    Sensory

    inputMotor

    outputIntegration

  • The nervous system of the vertebrates: Main components

    PNS: Groups of neurons (ganglia) and peripheral nerve tracks

    - somatic part

    - autonomous (vegetative) part - sympathic part

    - parasympathic part

    (Campbell et al.,

    Biologie)

  • Central nervous system (CNS): Brain

    The nervous system of the vertebrates: Main components

    forebrain midbrain hindbrain

    Forebrain: Telencephalon, Diencephalon (Thalamus, Hypothalamus)

    Midbrain: Mesencephalon (Tectum)

    Hindbrain: Metencephalon (Pons, Cerebellum), Myelencephalon

    (Medulla oblongata)

    Brainstem: Midbrain + Hindbrain - Cerebellum

  • CNS: Spinal cord

    - Segmented organization (31 paired

    spinal nerves in 4 major regions),

    - H-like structure: gray and surrounding

    white matter

    - Divided into dorsal and ventral horn and

    dorsal, lateral, and ventral

    columns(Kandel et al., Principles of Neural

    Science)

    Evolution and development

  • Somatic nervous system:

    Signals to skeletal muscle in response

    to external stimuli

    Autonomous (vegetative) nervous

    system: signals that affect the inner

    milieu (energy metabolism and

    homeostasis)

    Two subunits:

    Sympathicus: Increase in energy

    consumption, organism is prepared for

    action ("fight and flight")

    Parasympathicus: reduction of energy

    consumption, recovery ("rest and

    digest")

    Peripheral nervous system (PNS)

    (Kahle, Taschenatlas der Anatomie Band 3)

    The nervous system of the vertebrates: Main components

  • Main axes of the CNS

    (Kandel et al., Principles of Neural

    Science)

    The nervous system of the vertebrates: Main components

  • The nervous system of the vertebrates: The mouse as a

    model

  • The nervous system of the vertebrates: The mouse as a

    model

    > 99% of all genes have homolog in humans (a gene inherited in

    two species by a common ancestor) → disease model

    Diverse genetic tools: (conditional) transgenic, knockout, knock-in mouse

    models

    Complete genome information (2002)

    Limitations:

    - Rats are a better model for high blood pressure and atherosclerosis

    - Rabbits are physiologically more similar to humans

  • Fertilized egg Blastula Gastrulagrowth invagination

    Formation of the neural plate

    from the ectoderm along the

    axis of the embryo

    Evolution and development

    Nervous system

    multilayered structure of three

    germ layers:

    - ectoderm

    - mesoderm

    - endoderm

  • Evolution and development

    Central nervous system (CNS)

    Dorsally positioned tube-like

    nerve strand (produced by invagination of the

    neural plate)

    Posterior part

    → spinal cord

    Anterior part

    →Vesicles

    →Brain(Segmental structure,

    present in both hemispheres

    of the brain)

    (Kahle, Taschenatlas der Anatomie Band 3)

  • Principles of organization

    Mammal Body weight Brain weightRelative brain

    weight

    elephant

    greenland whale

    mouse

    man

    gorilla

    cat

    2047 kg

    62250 kg

    21 g

    60-72 kg

    95,5 kg

    4-5 kg

    4048 g

    2490 g

    0,4 g

    1300-1500 g

    425 g

    27,3-32 g

    0,2%

    0,004%

    1,9%

    2-2,3%

    0,46%

    0,64-0,68%

    (R. Nickel, A. Schummer, E. Seiferle, Lehrbuch

    der Anatomie der Haustiere Bd. 4, Parey)

    1. Increase in the relative size of the brain

  • 2. Increase in differentiation and segmentation

    Principles of organization

  • 3. Increase in complexity of the forebrain

    Principles of organization

  • 4. Increase in the surface of the cerebral cortex

    Principles of organization

  • 5. Separation in gray and white matter

    Functionality of the CNS requires optimization of two competing

    requirements:

    - high interconnectivity

    - short conduction delays

    → Solution: Segregation between gray and white matter:

    - High connectivity in small regions („local connections“) (maximal number of

    cells: about 10,000 neurons with tolerable delay (ms range) → gray matter

    - Fast connections with high conduction speed („global wiring“) → white matter

    (Lit.: Wen, Q., and Chlovskii, D.B. (2005) Segregation of the brain into gray and white

    matter: a design minimizing conduction delays. PLOS Computational Biol. 1: e78-

    e87.)

    Principles of organization

  • 6.Serial organization and orderly connections

    - Serial organization

    (relays); information is

    transformed at every step

    - Pathways that link the

    components (tracts, „Bahnen“)

    - Pathways cross to the other side

    (contralateral side) of the body at

    a certain anatomical level

    - Projections occur in an orderly

    fashion thus producing neural

    maps (somatotopy)

    (Kandel et al., Principles of Neural

    Science)

    Principles of organization

  • Total of 700 km of veins

    → Large surface (180 cm2/g brain):

    → Efficient gas exchange (O2, CO2)

    Blood supply

    Brain is highly vulnerable – anoxia and ischemia within the range of

    seconds cause neurologic symptoms and within the range of minutes

    irreversible damage of neurons (stroke)

    Blood and liquor system

  • (Kahle, Taschenatlas der Anatomie Band 3)

    Blood supply by four large

    arteries:

    - 2 Arteriae carotides

    internae

    - 2 Aa. vertebrales

    Blood supply

    Blood and liquor system

  • (Kahle, Taschenatlas der Anatomie Band 3)

    Cerebrospinal fluid (CSF)

    Blood and liquor system

    CNS is surrounded by Liquor

    cerebrospinalis including the four

    ventricles (about 140 ml) →

    provides cushion and buoyancy

    (Reduction of brain weight

    from 1400 g to 45 g)

  • Liquor cerebrospinalis is present in the subarachnoid space

    Secreted by the choroid plexus in the lateral ventricles

    Absorbed through the arachnoid membranes (purple;

    „Spinngewebshaut“) and transported through the arachnoid

    granules into the venous sinuses → provides a one-way system

    to remove harmful metabolites (turnover 3 times/24 hrs.)

    Composition of the

    CSF may be

    altered during

    disease →

    diagnostic tool

    (Kahle, Taschenatlas der Anatomie Band 3)

    Cerebrospinal fluid (CSF)

    Blood and liquor system

  • Cerebrospinal fluid (CSF)

    Blood and liquor system

  • 1st Goldmann-Experiment (Edwin Goldmann, 1909):

    IV (intravenous) Trypan blue injection → No staining of brain and spinal cord

    (Saunders et al., The rights and wrongs of

    blood-brain permeability studies“

    Frontiers in Neuroscience, 2014)

    Blood brain barrier

    Blood and liquor system

  • 2nd Goldmann experiment: Trypan blue injection into liquor room →

    only brain and spinal cord stain → blood-liquor barrier

    Blood brain barrier is present already

    early during embryonal

    development

    Blood brain barrier

    Blood and liquor system

  • (Campbell, Biologie)

    Blood brain barrier

    Blood and liquor system

  • Blood brain barrier

    Blood and liquor system

  • Blood brain barrier

    Blood and liquor system

    Tight junctions between endothelial cells formed under the influence of

    astrocytes

  • 1. Water-soluble substances do not

    pass through the blood-brain

    barrier

    2. Lipid-soluble substances pass

    through the blood-brain barrier

    Blood brain barrier

    Blood and liquor system

  • Disease: Hydrocephalus (accumulation

    of CSF) – genetic defect or caused

    by infection H. occlusus: blockage of foramina

    H. aresorptivus: decreased resorption by

    arachnoid membranes

    H. hypersecretorius: increased production

    Foramen interventriculare

    (Monroi)

    (Kahle, Taschenatlas der Anatomie Band 3)

    Blood brain barrier

    Blood and liquor system