Transcript Synapses and neuronal signalling

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 signallingGeneral
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
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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
Divergence
Convergence
• Each sensory fibre will
form nerve terminals on
multiple motor neurons
from several extensor
muscles (divergence)
• Multiple sensory nerves
will contact each motor
neuron allowing it to take
account of a wider range
of stretch information
(convergence)
Inhibitory interneurons act in feedforward 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
Membrane Potential
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0 mV
-6 5 mV
• Output of most neurons is
a pattern of spikes (action
potentials)
• Inside of neuronal
membrane is normally
electrically negative
• Action potential is a
transient depolarisation of
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
Amplit ude
Duration
Summative? Eff ect
Propagation
Receptor
potentia ls
0.1- 10mV
5-100msec
Graded
Passive
Synaptic
potentia ls
0.1-10mV
5msec20min
Graded
Actio n
potentia l
70-110mV
1-10msec
All or none
Hyper- or
Depolarising
Hyper- or
Depolarising
Depolarizin g
Passive
Activ e
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
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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