Sending messages in the nervous system

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Sending messages in the nervous system

• Karen Bryan
• Professor of Clinical Practice, Speech and
  Language Therapist.
• Head of the Division of Health and Social Care,
  Faculty of Health and Medical Sciences,
  University of Surrey. UK.

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Introduction

• In the last session we looked at basic anatomy
• Now going to consider how the structural elements
  work together to sed messages in the brain

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INTRODUCTION

• Along with muscle cells, neurons are unique in
  that they are excitable that is, they respond to
  stimuli by generating electrical impulses.
• Electrical responses of neurons (modifications of
  the electrical potential across their membranes)
  may be local (restricted to the place that
  received the stimulus) or propagated (may travel
  through the neuron and its axon).
• Propagated electrical impulses are termed action
  potentials.
• Neurons communicate with each other at synapses
  by a process called synaptic transmission.

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MEMBRANE POTENTIAL

• The membranes of cells, including nerve cells,
  are structured so that a difference in electrical
  potential exists between the inside (negative)
  and the outside (positive). This results in a
  resting potential across the cell membrane, which
  is normally about -70 mV.

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Action potentials

• Neurons communicate by producing electrical
  impulses called action potentials.
• Action potentials are self-regenerative
  electrical signals that propagate throughout a
  neuron and along its axon.
• The action potential is a depolarization of about
  100 mV (a large signal for a neuron). The action
  potential is all or none. Its size is constant
  for each neuron.
• As the impulse passes, repolarization occurs
  rapidly at first and then more slowly. Membrane
  potential thus returns to resting potential. The
  action potential tends to last for a few
  milliseconds.

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Myelination and transmission

• Nonmyelinated axons, in the mammalian PNS and
  CNS, generally have a small diameter (less than 1
  um in the PNS and less than 0.2 um in the CNS).
  The action potential travels in a continuous
  manner along these axons. Myelinated axons, are
  covered by myelin sheaths. The myelin has a high
  electrical resistance and low capacitance,
  permitting it to act as an insulator. The myelin
  sheath is not continuous along the entire length
  of the axon. On the contrary, it is periodically
  interrupted by small gaps, called the nodes of
  Ranvier, where the axon is exposed. The signal
  can therefore jump from one node to the next.
• What does this give us?

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Synapses

• Synapses are the junctions between neurons that
  permit them to communicate with each other.

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Synapse works via neurotransmitters

• Acetylcholine (ACh) is the transmitter at this
  synapse.
• Ach is produced in response to the action
  potential.
• The released ACh diffuses rapidly across the
  synaptic cleft
• Binds to postsynaptic ACh receptors where
  depolarizes the membrane.
• When the channel closes, the ACh dissociates and
  is hydrolyzed by acetylcholinesterase

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Neuro-muscular junction

• The axons of lower motor neurons project through
  peripheral nerves to muscle cells.
• These motor axons terminate at a specialized
  portion of the muscle membrane called the motor
  end-plate,
• The nerve impulse is transmitted to the muscle
  across the neuromuscular junction or synapse.
• The transmitter at the neuromuscular synapse is
  Ach which triggers nerve impulses
• When the impulses exceed the end-plate potential
  the muscle fibre is activated.

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Neurotransmitters

• A large number of molecules act as
  neurotransmitters at chemical synapses. See table
  next.
• These neurotransmitters are present in the
  synaptic terminal, and their action may be
  blocked by pharmacologic agents.
• Some presynaptic nerves can release more than one
  transmitter differences in the frequency of
  nerve stimulation probably control which
  transmitter is released.

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Acetylcholine

• ACh is synthesized by choline acetyltransferase
  and is broken down after release into the
  synaptic cleft by acetylcholinesterase (AChase).
• ACh acts as a transmitter at a variety of sites
  in the PNS and CNS eg excitatory transmission at
  the neuromuscular junction
• In Alzheimer's disease cholinergic neurons in the
  basal forebrain nucleus degenerate, and their
  cholinergic terminals in the cortex are lost

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Glutamate

• The amino acid glutamate has been identified as a
  major excitatory transmitter in the mammalian
  brain and spinal cord.
• Because glutamate is an excitatory transmitter,
  excessive glutamate release may be important in
  acute neurologic disorders, such as stroke and
  CNS trauma, and possibly in some chronic
  neurodegenerative diseases, such as Alzheimer's.

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Catecholamines

• The catecholamines noradrenaline, adrenaline
  and dopamine are formed from the essential amino
  acid phenylalanine.
• Fight or flight response!

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Dopamine

• Dopaminergic neurons generally have an inhibitory
  effect.
• Dopamine-producing neurons project from the
  substantia nigra to the caudate nucleus and
  putamen, and from the the limbic system to the
  cortex.
• In Parkinson's disease, there is degeneration of
  the dopaminergic neurons and the substantia
  nigra. Thus, the inhibition of neurons in the
  caudate nucleus and putamen is impaired.
• The dopaminergic projection to the limbic system
  and cortex may be involved in schizophrenia
• Antipsychotic drugs such as phenothiazines act as
  dopamine receptor antagonists and can temporarily
  reduce psychotic behavior in some patients with
  schizophrenia.

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Serotonin

• Serotonin (5-hydroxytryptamine) is an important
  regulatory amine in the CNS. Serotonin-containing
  neurons are present in the pons and medulla.
  These cells are part of the reticular formation,
  and they project widely to the cortex and
  hippocampus, basal ganglia, thalamus, cerebellum,
  and spinal cord.
• Serotonin has vasoconstrictor and pressor
  effects. Some drugs (eg, reserpine) may act by
  releasing bound serotonin within the brain.
• In small doses, (LSD), a structural analog of
  serotonin, is capable of evoking mental symptoms
  similar to those of schizophrenia.
• Serotonin-containing neurons, along with
  norepinephrine-containing neurons, appear to play
  an important role in determining the level of
  arousal. Serotonin-containing neurons may also
  participate in the modulation of sensory input,
  particularly for pain. Selective serotonin
  reuptake inhibitors, which increase theamount of
  Serotoinin are used to treat some forms of
  depression.
• Issues around illegal drugs and brain chemistry!

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Endorphins

• Endorphins refers to some morphine-like
  substances whose activity has been defined by
  their ability to bind to opiate receptors in the
  brain.
• Endorphins (brain polypeptides with actions like
  opiates) may function as synaptic transmitters or
  modulators.
• Endorphins appear to modulate the transmission of
  pain signals within sensory pathways. When
  injected into animals, endorphins can be
  analgesic and tranquilizing.

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Clinical cases 1

• NeuropathyIn peripheral neuropathies (diseases
  affecting peripheral nerves) the conduction
  velocity of motor nerves may be reduced. The
  reduction in conduction velocity can be measured
  in terms of increased conduction time between
  nerve stimulation and muscle contraction. Slowing
  in conduction velocity occurs in neuropathies
  when there is demyelination, such as in
  Guillain-Barre syndrome.
• Patients have very rapid onset of tiredness,
  movement difficulty, breathing difficulty.

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Clinical cases 2

• Demyelination, or damage to the myelin sheath, is
  seen in a number of neurologic diseases. The most
  common is multiple sclerosis, in which myelin
  within the brain and spinal cord is damaged as a
  result of abnormal immune mechanisms. As a result
  of loss of myelin insulation, the conduction of
  action potentials is slowed or blocked in
  demyelinated axons.
• Deteroration occurs sporadically as demyelination
  occurs affecting often vision, movement, bladder
  control, more rarely cognition.