NEURONS AND GLIA

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NEURONS AND GLIA
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Introduction

• Neurophilosophy
• Brain (neurons) is the origin of mental abilities
• Glia and Neurons
• Glia
• Insulates, supports, and nourishes neurons
• 90 of brain cells are glial cells
• Neurons
• Process information
• Sense environmental changes
• Communicate changes to other neurons
• Command body response

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The Neuron Doctrine

• The birth of neurohistology
• Microscopy invention
• Discovery of fixation method for cutting thin
  slices
• Staining methods for selectively coloring parts
  of cells

• The Nissl Stain
• Developed by by the German neurologist Franz
  Nissl
• Stain the nuclei and surrounding material (Nissl
  body)
• Made it possible to distinguish neurons vs. glia
  and to study the arrangements of neurons in
  different parts of brain (cytoarchitecture)

Fig2.1
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The Neuron Doctrine

• The Golgi Stain
• Camillo Golgi discovered that by soaking brain
  tissue in a silver chromate solution, a small
  percentage of neurons became darkly colored in
  their entirety
• Soma (cell body or perikaryon) and neurites
  (axons and dendrites)

Fig 2.3
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The Neuron Doctrine

• Cajals Contribution
• Santiago Ramon y Cajal used Golgi stain method
  and worked out the circuitry of many regions of
  the brain Father of neuroanatomy
• Golgi versus Cajal
• Reticular theory vs. cell theory

• Neuron doctrine
• Neurons communicate by contact, not continuity
• Final proof had to wait until EM got developed in
  the 1950s

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The Prototypical Neuron

• The Soma
• 20 um in diameter
• Cytosol Potassium rich watery fluid inside the
  cell
• Organelles Membrane-enclosed structures within
  the soma
• Cytoplasm Contents within a cell membrane (e.g.,
  organelles, excluding the nucleus)

Fig2.7
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The Prototypical Neuron

• The Axon
• Begins with axon hillock, initial tapered segment
  where action potentials are generated
• Rough ER does not extend into axon
• Protein composition of axon membarane is
  fundamentally different from that of soma
• No protein synthesis in the axon
• May extend from less than a millimeter to over a
  meter long
• May branch out (generally at right angles) to
  form axon collaterals that could return to the
  same cell (recurrent collaterals)
• Diameter ranges from less than 1 mm to 25 mm in
  humans - The speed of nerve impulses depends on
  axonal diameter

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The Prototypical Neuron

• The Axon Terminal (terminal bouton)
• A site where the axon comes in contact with other
  neurons and passes information on to them
• Terminal arbor or boutons en passant
• Synapse - To fasten together
• Innervation - making synaptic contact
• Differences between the cytoplasm of axon
  terminal and that of axon
• No microtubules in the terminal
• Presence of synaptic vesicles (50 nm in
  diameter)
• Dense covering of proteins on the inside surface
  of the synaptic membrane
• Large number of mitochondria (high energy demand)

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The Prototypical Neuron

• Synapse
• Pre- and Postsynaptic sides directionality of
  information flow
• Synaptic transmission
• Synaptic cleft
• Electrical-to-chemical-to-electrical
  transformation
• Neurotransmitter

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The Prototypical Neuron

• Axoplasmic transport
• Wallerian degeneration
• Degeneration of axon when severed (axotomy) is
  due to the lack of protein synthesis machinery
  within axon

Kandel Fig 55-18

• Anterograde transport by kinesin and retrograde
  transport by MAP-1C (dynein)

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The Prototypical Neuron

• Slow Axoplasmic transport
• Paul Weisss experiment
• Tied off a sciatic nerve (axon) to find that
  material accumulate on the proximal side of the
  knot
• When the knot was untied, the bulged out
  accumulation continued down the axon
• The speed of movement was measured to be about 1
  - 10 mm per day SLOW AXOPLASMIC TRANSPORT
• Only anterograde direction
• Slow transport itself can be at two different
  speeds
• Slower (0.2-2.5mm per day) fibrillar elements
  of cytoskeleton (neurofilament subunits,
  tubulins..)
• Faster (about twice as fast as the slower)
  various cytosolic proteins (clathrin, actin,
  actin-binding proteins, enzymes..)

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The Prototypical Neuron

• Fast Axoplasmic transport
• Bernice Grafstein
• Injected radioactive amino acids into somata
• Traced the synthesized (hot) proteins along the
  axon

• Large membraneous organelles are transported via
  fast transport
• Includes vesicles of the constitutive secretory
  pathways, synaptic vesicles precursor membranes,
  mitochondria, smooth ER elements..
• ATP dependent but not protein synthesis dependent
  (once synthesized)
• Soma-independent (isolated axon still can
  transport

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The Prototypical Neuron

• Dendrites
• Greek for tree
• Dendritic tree for all the dendrites of a neuron
• Antennae of neurons - covered with thousands of
  synapses
• Dendritic membrane (postsynaptic membrane)
  contains many specialized receptors for
  neurotransmitters
• Dendritic spines
• Some neurons have these structures for receiving
  some types of inputs
• Discovered by Cajal
• Believed to isolate various chemical reactions
• Dynamic structures affected by the type and
  amount of inputs and developmental changes of
  environment

Fig 2.17
Fig 2.18
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• Mental Retardation and dendritic spines
• Brain function depends on the highly precise
  synaptic connections, which are formed during the
  fetal period and are refined during infancy and
  early childhood
• 95 of population falls within two standard
  deviations from the mean of IQ (around 70 when
  the mean is set to be 100). Some 2-3 of humans
  with intelligence score below are considered to
  be mentally retarded IF the cognitive impairment
  affects the persons ability to adapt their
  behavior to the setting in which they live

• Can have many causes
• Genetic disorders such as PKU or Down syndrome
• Accidents or infection during pregnancy or early
  childhood
• Poor nutrition during pregnancy
• Environmental impoverishment such as the lack of
  good nutrition, socialization, sensory
  stimulation during infancy
• Some with clear physical correlates (retarded
  growth, abnormal structures of head, hands, and
  body), most with only behavioral manifestations
• Dendritic spine abnormality has been found to be
  correlated with mental retardation

Fig A
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Classifying Neurons

• Classification Based on the Number of Neurites
• Unipolar cell
• Found in invertebrate nervous system - single
  process with different segments serving as
  receptive surfaces or releasing terminals
• Bipolar cell
• Two neurites
• Multipolar cell
• Most neurons in the brain are multipolar

Kendal fig 2-4
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Classifying Neurons

• Classification Based on Dendritic and Somatic
  Morphologies
• Often unique to a particular region of the brain
• Cortex - Stellate cells (star-shaped) and
  pyramidal cells (pyramid-shaped)
• Spiny or aspinous

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Classifying Neurons

• Further Classification
• Based on connections within the CNS
• Primary sensory neurons
• motor neurons
• interneurons
• Based on axonal length
• Golgi Type I - projection neurons that extend
  their axons to other parts of the brain (e.g.
  pyramidal neurons in the cortex)
• Golgi Type II - local circuit neurons that have
  short axons that do not extend beyond the
  vicinity of cell body (e.g. stellate cells in
  the cortex)
• Based on neurotransmitter type
• Cholinergic, glutamatergic, GABAergic

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Glia

• Sleeping Giants ?
• Function of Glia
• Supports neuronal functions
• Without glia brain cannot function!
• Astrocytes
• Most numerous glia in the brain
• Fill spaces between neurons
• Imporatant regulator of the chemical contents of
  extracellular spaces (Not much left after filling
  up)
• Envelop synaptic junctions - restrict the
  spreading of released neurotransmitters
• Possess their own neurotransmitter receptors!!

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Glia

• Myelinating Glia
• Oligodendroglia (in CNS) and Schwann cells (in
  PNS)
• Insulate axons by wrapping axons around
• Myelin sheath
• One Oligodedroglia can provide insulation to
  several axons but each Schwann cell does to a
  only a single axon
• Node of Ranvier
• Region where the axonal membrane is exposed

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Glia

• Other Non-Neuronal Cells
• Microglia as phagocytes (immune)
• Ependymal cells provide lining of fluid-filled
  ventricles and directs cell migration during
  brain development
• Vasculature