How Neurons Work

1
How Neurons Work

• Nancy Alvarado, Ph.D.
• Dr. Goldmans PSY 210 Class
• April 16, 2003

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Two Kinds of Cells

• Neurons (nerve cells) signaling units
• Glia (glial cells) supporting elements
• Separate and insulate groups of neurons
• Produce myelin for the axons of neurons
• Scavengers, removing debris after injury
• Buffer and maintain potassium ion concentrations
• Guide migration of neurons during development
• Create blood-brain barrier, nourish neurons

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Neuronal Circuits

• Neurons send and receive messages.
• Neurons are linked in pathways called circuits
• The brain consists of a few patterns of circuits
  with many minor variations.
• Circuits can connect a few to 10,000 neurons.

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Parts of the Neuron

• Soma the cell body
• Neurites two kinds of extensions (processes)
  from the cell
• Axon
• Dendrites
• All parts of the cell are made up of protein
  molecules of different kinds.

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How Neurons Communicate

• An electrical signal, called an action potential,
  is propagated down the axon.
• An action potential is an all-or-nothing signal.
• The amplitude (size) of the action potential
  stays constant because the signal is regenerated.
• The speed of the action potential is determined
  by the size of the axon.
• Action potentials are highly stereotyped (very
  similar) throughout the brain.

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How to Tell Axons from Dendrites

• Dendrites receive signals axons send them.
• There are hundreds of dendrites but usually just
  one axon.
• Axons can be very long (gt 1 m) while dendrites
  are lt 2 mm.
• Axons have the same diameter the entire length
  dendrites taper.
• Axons have terminals (synapses) and no ribosomes.
  Dendrites have spines (punching bags).
• Dont be fooled by the branches both have them.

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Ramon y Cajals Principles

• Principle of dynamic polarization electrical
  signals flow in only one, predictable direction
  within the neuron.
• Principle of connectional specificity
• Neurons are not connected to each other, but are
  separated by a small gap (synaptic cleft).
• Neurons communicate with specific other neurons
  in organized networks not randomly.

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Ways of Classifying Neurons

• By the number of neurites (processes)
• Unipolar, bipolar, multipolar
• By the type of dendrites
• Pyramidal stellate (star-shaped)
• By their connections (function)
• Sensory, motor, relay interneurons, local
  interneurons
• By neurotransmitter by their chemistry

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Parts of the Soma (Cell Body)

• Nucleus stores genes of the cell (DNA)
• Organelles synthesize the proteins of the cell
• Cytosol fluid inside cell
• Plasmic membrane wall of the cell separating it
  from the fluid outside the cell.

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Organelles

• Mitochondria provide energy
• Microtubules give the cell structure
• Rough endoplasmic reticulum produces proteins
  needed to carry out cell functioning
• Ribosomes produce neurotransmitter proteins
• Smooth endoplasmic reticulum packages
  neurotransmitter in synaptic vesicles
• Golgi apparatus Part of the smooth endoplasmic
  reticulum that sorts proteins for delivery to the
  axon and dendrites

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Kinds of Glia

• Oligodendrocytes surround neurons and give them
  support.
• In white matter, provides myelination
• In gray matter, surround cell bodies
• Schwann cells provide the myelin sheath for
  peripheral neurons (1 mm long).
• Astrocytes absorb potassium, perhaps nutritive
  because endfeet contact capillaries (blood
  vessels), form blood-brain barrier.

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Four Signals Within the Neuron

• Input signal occurs at sensor or at points
  where dendrites are touched by other neurons.
• Integration (trigger) signal occurs at first
  node (in sensory neuron) or at axon hillock.
• Conducting signal travels down axon.
• Output signal releases neurotransmitter at axon
  terminal.

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The Neuron at Rest

• Neurons have potassium (K) inside and sodium
  (Na) outside in the extracellular fluid.
• Ion channels in the cell wall (membrane) are
  selectively permeable to potassium, sodium or
  calcium.
• Ion pumps maintain the cells inner environment.

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How Ions Cross the Membrane

• Diffusion an ionic concentration gradient
  exists
• Differences in electrical membrane potential and
  equilibrium potential
• Ionic driving force
• Ion pumps
• Sodium/potassium, calcium

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The Action Potential

• Depolarization influx of sodium (Na) or
  another positive ion makes the membrane potential
  more positive.
• When the membrane potential reaches threshold,
  voltage-gated Na ion channels open.
• After 1 msec, voltage-gated K channels open,
  polarizing the neuron again.
• Sodium-potassium pump helps restore neuron to its
  resting potential.
• Resting potential is polarized, typically -65 mV

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Conduction Down the Axon

• Rapid depolarization in one spot causes membrane
  just ahead to depolarize too.
• Speed of conduction depends on the size of the
  axon and the number of ion channels.
• Myelin permits the action potential to travel
  rapidly from node to node by blocking the
  membrane between nodes.
• Ion channels occur at the nodes, permitting an
  influx of Sodium to regenerate the action
  potential.

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Graded Response

• If action potentials are all-or-nothing and
  always have the same amplitude (size), how is a
  graded response produced?
• More intense and longer duration stimuli produce
  more frequent action potentials.
• More frequent action potentials release more
  neurotransmitter.
• More neurotransmitter increases the likelihood
  the next neuron will have an action potential.

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Two Kinds of Neural Activity

• Excitatory causes another neuron to be more
  likely to fire (have an action potential).
• Inhibitory causes another neuron to become
  hyperpolarized (more negatively charged), making
  it less likely to fire.

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Interpretation of the Signals

• Action potentials are the same in neurons all
  over the brain.
• The meaning of an action potential comes from the
  interconnections among the neurons, not from the
  action potential itself.
• It is the flow of information through a network
  that is important -- what is connected to what.
• Connectionist models try to simulate this
  approach using computer software.

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Differences Among Neurons

• Some local interneurons do not generate action
  potentials because their axons are short.
• Some neurons do not have a steady resting
  potential and are spontaneously active.
• Neurons differ in the types and combinations of
  ion channels in their cell membranes.
• Neurons differ in their neurotransmitters
  released and their receptors for transmitters.

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Consequences for Disease

• The nervous system has more diseases than any
  other organ of the body.
• Some diseases attack a particular kind of neuron
  (e.g., motor neurons in ALS polio).
• Parkinsons attacks certain interneurons using a
  particular neurotransmitter (dopamine).
• Some diseases affect only parts of the neuron
  (e.g., cell body, axon).

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Ion Channels
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Ion Channels

• Found in all cells throughout the body.
• Open and close in response to signals.
• Selectively permeable to specific ions
• High rate of flow (conductance)
• Resting channels usually open
• Gated channels open and close
• Refractory period temporarily cannot be opened

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Control of Gating

• Binding of neurotransmitters, hormones, or second
  messengers from within the cell.
• Phosphorylation energy comes from a phosphate
  that binds with the channel.
• Dephosphorylation removal of the phosphate.
• Voltage-gated responds to a change in the
  membrane potential.
• Stretch or pressure gated mechanical forces.

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Kinds of Receptors

• All neurotransmitters bind and act at more than
  one kind of receptor.
• Two main kinds of receptors
• Ion channel receptors
• G-protein-coupled receptors

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G-Protein-Coupled Receptors

• Change the excitability of the neuron in two
  ways
• Change calcium ion levels (releasing
  neurotransmitter).
• Activate intra-cellular second messengers
• Signal amplification
• Signaling at a distance
• Cascades of activation
• Long-lasting chemical changes in neuron

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Importance of Calcium

• Voltage-gated calcium (CA2) channels permit CA to
  enter the cell.
• As CA2 rises, it binds with the neuron,
  preventing additional calcium from entering.
• Increased calcium concentrations can cause
  dephosphorylation or permanent inactivation of a
  channel.
• Calcium signals neurotransmitter release.

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Effects of Drugs

• Exogenous ligands drugs that come from outside
  the body.
• Endogenous ligands naturally occurring
• Agonist binds with and opens a channel.
• Endogenous or exogenous (e.g., drug)
• Antagonist binds with and closes a channel.
• Reversible (curare) or irreversible (snake venom)

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Kinds of Neurotransmitters

• Amino acids amines
• GABA, Glycine (Gly), Glutamate (Glu)
• GABA is inhibitory, Glu is excitatory
• Strychnine blocks GABA receptors interfering with
  inhibition so excitations overwhelm the brain.
• Monoamines
• Cholinergic Acetylcholine (ACh), used by
  muscles
• Catecholaminergic regulate thinking, mood

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Kinds of Neurotransmitters (Cont.)

• Catecholamines synethesized from tyrosine
• Dopamine
• Norepinephrine (Noradrenaline)
• Epinephrine (Adrenaline) -- widespread
• Serotonin (5-HT) broken down by MAO, LSD binds
  at receptors.
• Peptides
• Oxytocin vasopressin
• Opioids (endorphins)