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Neuronal signalling

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					  Neuronal signalling- 3 lectures
             Dr Bill Phillips, Dept of Physiology

• Synapses and neuronal signalling
• Local signalling in neurons
• Excitability and Initiation of neuronal
  signals
• Kandel, Schwartz & Jessell, Principles of Neural Science
  4th Edn Cpts 2,7,8,9
     Synapses and neuronal signalling-
                 General
             Dr Bill Phillips, Dept of Physiology
• Neuronal connections and their activity patterns give rise
  to behaviour
• Glial function
• The 4 functional domains within a neuron
• Signalling networks underlie specific behaviours
• Electrical nature of neuronal signalling
• Different types of information are conveyed using similar
  signals carried by distinct pathways
• Gene expression creates diversity and change in neuronal
  function
Neuronal connections and their activity
   patterns give rise to behaviour

   Sensation               Interneuron network
                           activity

                                 Central processing

    Motor response
                     Motor system interneuron
                     activity
                   Glial functions
•   Structural support and insulation of neurons
•   Myelin sheaths- Oligodendrocytes & Schwann
•   Scavenging dead cells- microglia
•   Housekeeping tasks- eg uptake of released
    neurotransmitters
•   Radial glia direct migration of developing neurons
•   Regulating the properties of presynaptic nerve terminals
•   Blood brain barrier- astrocytes
•   Trophic support for neurons?
 The 4 functional domains within a
              neuron
• Input region/s for depolarising membrane
  currents (excitatory synapses or sensory
  receptor channels)
• Trigger zone integration of depolarising
  signals to initiate action potentials or not
• Propagation region- axon or sensory fibre
• Chemical release zone- transmitter or
  hormone release terminal
Signalling networks underlie specific
             behaviours
• Specific information processing tasks arise out of
  patterns of interconnections among neurons
• Both excitatory and inhibitory connections are
  involved in achieving functional outcomes
• Simple reflex responses are organised within
  spinal segments but sensory information is also
  fed to higher centres
Knee jerk reflex
        • Sensory receptors in
          extensor muscle send
          signals centrally in
          response to stretch
        • Excitatory (+ve) inputs to
          activate motor neurons to
          the extensor muscles
        • Other sensory nerve
          terminals activate
          inhibitory interneurons
          that inhibit flexor motor
          neurons
  Converging and Diverging inputs:
common features of neuronal networks
                           • Each sensory fibre will
                             form nerve terminals on
                             multiple motor neurons
                             from several extensor
                             muscles (divergence)
                           • Multiple sensory nerves
                             will contact each motor
Divergence   Convergence     neuron allowing it to take
                             account of a wider range
                             of stretch information
                             (convergence)
    Inhibitory interneurons act in feed-
     forward and feed-back inhibition
• Feed-forward eg. Stretch afferent from extensor
  muscle acts through interneuron to inhibit activity
  of flexor motor neuron
• Feedback eg. Diverging axon branch of extensor
  motor neuron activates inhibitory interneuron that
  acts back to reduce firing of the motor neuron
Feed-forward
inhibition




Feed-back
inhibition
                                Electrical nature of neuronal
                                          signalling
                                               • Output of most neurons is
                                                 a pattern of spikes (action
                                                 potentials)
.
    Membrane Potential




                                               • Inside of neuronal
                         0 mV
                                                 membrane is normally
                                                 electrically negative
                                               • Action potential is a
                                                 transient depolarisation of
                     -6 5 mV




                                                 the cell membrane
Membrane is polarised at rest
      Action Potentials: Basic
            mechanism
• Depolarisation at trigger zone initiates
  Hodgkin Cycle in local population of
  voltage-gated Na+ channels (and/or Ca2+
  channels)
• Na+ channel inactivation
• Delayed opening of voltage-gated K+
  channels in response to depolarisation
Range of sensation is encoded in
   the frequency of ‘spikes’
• If the trigger zone of a neuron is depolarised
  to ‘threshold’ one or more action potentials
  are initiated and propagate along the nerve
  fibre
• Action potentials typically occur in ‘trains
  of spikes (action potentials)
• The frequency of spikes is often determined
  by the degree of depolarisation.
       Passive, triggering potentials vs
             the action potential
Signal type   Amplitude   Duration    Summative? Effect          Propagation



Receptor      0.1- 10mV   5-100msec   Graded        Hyper- or    Passive
potentials                                          De-
                                                    polarising
Synaptic      0.1-10mV    5msec-      Graded        Hyper- or    Passive
potentials                20min                     De-
                                                    polarising
Action        70-110mV    1-10msec    All or none   De-          Active
potential                                           polarizing
 Different types of information are conveyed using
    similar signals carried by distinct pathways

• For sensory, motor and inter-neurons the
  nature of the signals (trains of spikes) is the
  same.
• Meaning of the signals is maintained by the
  distinct pathways of nerve fibres and their
  target nuclei in the brain.
Gene expression creates diversity
and change in neuronal function
• Neurons differ most in the genes that they express
• Different combinations of ion channels,
  transmitter receptors
• Enzymes and genes for different transmitters
• Other proteins that influence excitability and
  synaptic function, adaptability
• Changes in expression of particular genes can
  modify the strength of particular synaptic inputs
  and outputs to alter behaviour of a neural network
 Propagation of neuronal signals
           Dr Bill Phillips, Dept of Physiology

• Ion channels underlying action potential
  depolarisation and repolarisation
• Continuous and saltatory propagation
• Passive spread of depolarisation between Nodes of
  Ranvier
• Properties of the Nodes and Internodes
• Disorders affecting action potential propagation eg
  Multiple Sclerosis
     Local signalling in neurons
• Active maintenance of the resting membrane potential
• Depolarising and hyperpolarising currents
• Input resistance of neurons determines the magnitude of
  passive changes in membrane potential
• Membrane capacitance prolongs the timecourse of signals
• Membrane and cytoplasmic resistance affect the efficiency
  of the spread of depolarising pulses
• Speed and efficiency of action potential propagation
  determined by passive membrane properties and axon
  diameter.
    Active maintenance of the resting
          membrane potential
• Resting membrane potential of a neuron is
  maintained by a constant slow diffusion of
  K+ out of the cell and Na+ into the cell.
• Resting potential lies close to the Nernst
  Potential for K+ the permeability of the
  resting membrane for K+ is ~20fold greater
  than for Na+
    Initiation of neuronal signals
          Dr Bill Phillips, Dept of Physiology

• Resting membrane potential
• Excitatory and inhibitory currents/potentials
• Passive properties of input parts of neurons
• Trigger zones and summation of synaptic
  potentials
• Role of inhibitory synapses
• Disturbances of neuronal excitability- eg
  epilepsy
  Synapses I: Presynaptic mechanisms
           Dr Bill Phillips, Dept of Physiology

• Ca2+ dependency of presynaptic neurotransmitter
  release processes
• Machinery of transmitter exocytosis
• Nature of the release event
• Vesicle recycling
• Presynaptic inhibition and autoinhibition
• Facilitation, potentiation of transmitter release
 Synapses II: Postsynaptic Mechanisms
          Dr Bill Phillips, Dept of Physiology

• Types of ligand gated channels and their
  properties
• The dendritic spine as a receptor station for
  glutamate
• NMDA and non-NMDA glutamatergic responses
• Developmental and plastic changes at spine
  synapses
• Inhibitory GABAA and glycine receptor synapses
      Neuromuscular disorders
           Dr Bill Phillips, Dept of Physiology

• Presynaptic acetylcholine release characteristics of
  the neuromuscular junction
• Postsynaptic membrane specialisations
• Synaptic acetylcholinesterase
• Myasthenia Gravis: causes and treatment
• Congenital Myasthenias- genes and synaptic
  function
• Prospects

				
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posted:4/9/2008
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