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Lecture 4

NEUROSC 10 Lecture Notes - Lecture 4: Parallel Computing, Botulism, Connexon


Department
Neuroscience
Course Code
NEUROSC 10
Professor
Babiec
Lecture
4

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What%Happens%Postsynaptically?
A%ligand%binds%to%a%receptor
Ligand-gated%Ion%Channels
Neurotransmitter%binds
1.
Channel%opens
2.
Ions%flow%across%membrane
Can%either%depolarize%the%cell%or%it%can%have%a%
hyperpolarizing%effect%(inhibitory)
a)
3.
Typical%ions%that%are%passed%include%Na+,%K+,%Ca2+,%Cl-
§
Metabotropic%%Receptors
Neurotransmitter%binds
1.
It's%a%protein%on%the%membrane%(that%uses%intermediate%
molecules%to%effect%change%in%the%postsynaptic%neuron)%
Able%to%signal%
G-protein%is%activated
2.
G-protein%subunits%or%intracellular% messengers%modulate%
ion%channels
3.
Ion%channel%opens
4.
Ions%flow%across%membrane
5.
Have%slow%responses
§
Generating%Postsynaptic%Potentials
In%the%absence%of%neurotransmitter,%the%ion%channel%is%normally%
closed
When%neurotransmitter%binds%to%extracellular% sites%on%the%receptor,%
it%induces%a%conformational%change%in%the%receptor%protein%that%
opens%the%channel%to%pass%ions
The%resulting%changes%in%membrane%potential%is%considered
Excitatory:%membrane%potential%rises%toward%threshold
§
Inhibitory:%membrane%potential%is%lowered%from%threshold
§
Excitatory%Postsynaptic%Potential
Na+%passes%through%ion%channels
§
Depolarization%occurs
§
Inhibitory%Postsynaptic%Potential
Cl-passes%through%ion%channels
§
Dendrites%use%passive%conduction%to%transmit%PSPs%to%the%soma%(cell%body)%
and%axon%initial%segment
If%the%EPSP%is%large%enough%when%it%gets%to%the%axon%initial%segment,%an%
action%potential%results
IPSPs%resist%membrane%depolarization
Synaptic%summation%is%usually%required%to%generate%an%action%potential
Types%of%Synaptic%Summation
Spatial
§Simultaneous%input%from%multiple%synapses%sum%to%generate%a%
larger%EPSP
Temporal
§Rapid%succession%of%EPSPs%at%the%same%synapse%sum%to%
depolarize%the%neuron%more%than%a%single%EPSP%would%have
Summary%of%Chemical%Synaptic%Transmission
Neurotransmitter%release
Receptor%binding
Ion%channels%open%or%close
Conductance%change%causes%current%flow
Postsynaptic%potential%changes
Postsynaptic%cells%excited%or%inhibited
Summation%determines%whether%or%not%an%action%potential%occurs
Toxins%blocking%synaptic%transmission:%tetrodotoxin
Na+%channel%blocker%-blocks%action%potentials
Found%in%a%variety%of%marine%and%terrestrial%animals
Causes%paralysis,%loss%of%sensation,%cardiac%arrhythmias
Death%normally%due%to%respiratory%depression
Toxins%blocking%synaptic%transmission
Botulism
§Paralysis%of%peripheral%neuromuscular%junctions,%including%
diaphragm%and%other%respiratory%muscles
Tetanus%("lockjaw")
§Blocks%inhibitory%transmission%from%interneurons%in%spinal%cord%
producing%hyper%excitation%of%skeletal%muscle
Impair%vesicular%release%with%primary%effects%at%different%synapses
Electrical% Synapses%Do%Exist:%Gap%Junctions
Gap%junctions%are%made%of%paired%channels%called%connexons
One%channel%of%the%pair%is%in%the%presynaptic%neuron%-the%other%in%
the%postsynaptic%neuron
Connexon%pore%is%much%larger%than%the%pore%of%ion%channels
A%variety%of%substances%can%diffuse%between%the%cytoplasm%of%the%
pre-and%postsynaptic%neurons,%e.g.%ions,%ATP,%sugars,%"second%
messengers"
Electrical% Synapses:%bidirectional
Allow%ionic%current%to%flow%passively%from%one%neuron%to%another
Transmission%is%extraordinarily%fast
Fulfill%critical%roles%at%"escape"%synapses%and%in%synchronizing%activity%
in%networks%of%neurons
Not%all%synapses%are%from%axons%to%dendrites
Axodendritic
Axosomatic
Axoaxonic%
Synaptic%Circuits
Convergence:%many%signals%lead%to%one%neuron
Divergence:%one%signal%splits%into%many
Serial%processing
Parallel%processing
Synaptic%Circuits:%"Canonical"%excitatory%circuits
Feeds%forward
§Sequential
Feedback
§Loop
§Recurrent%excitation
Different%Ways%that%Feedback%and%Inhibition%can%occur
Feedback%can%trigger%inhibition
Presynaptic%Inhibition
§Turns%off%before%the%signal%even%gets%to%the%postsynaptic%
neuron
§Stops%the%pre-synapse%before%even%starting
Feedforward%Inhibition
§The%signal%goes%through,%then%the%channel%switches%off
Recurrent%Inhibition
§Axon-axon
§Shoots%out%inhibition%trigger%repeatedly%and%might%prevent%
axon%from%sending%off%an%action%potential
Complex%functionality%arises%quickly%from%combining%excitatory%and%
inhibitory%synapses
The%Neuron%Doctrine%and%Theory%of%Dynamic%Polarization%Revisited
Electrical% synapses
Dendrodendritic,%axodendritic,%axoaxonic%synapses
§Violate%the%theory%of%dynamic%polarization
§Leave%open%the%possibility%that%for%certain%types%of%synaptic%
signaling%in%certain%parts%of%the%brain%leave%out%the%soma%and%
integration%of%signals%altogether
10/16%Lecture
Monday,%October%16,%2017
4:05%PM
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What%Happens%Postsynaptically?
A%ligand%binds%to%a%receptor
Ligand-gated%Ion%Channels
Neurotransmitter%binds1.
Channel%opens2.
Ions%flow%across%membrane
Can%either%depolarize%the%cell%or%it%can%have%a%
hyperpolarizing%effect%(inhibitory)
a)
3.
Typical%ions%that%are%passed%include%Na+,%K+,%Ca2+,%Cl-
Have%fast%responses
§
Metabotropic%%Receptors
Neurotransmitter%binds1.
It's%a%protein%on%the%membrane%(that%uses%intermediate%
molecules%to%effect%change%in%the%postsynaptic%neuron)%
Able%to%signal%
G-protein%is%activated2.
G-protein%subunits%or%intracellular% messengers%modulate%
ion%channels
3.
Ion%channel%opens4.
Ions%flow%across%membrane5.
Have%slow%responses
§
Generating%Postsynaptic%Potentials
In%the%absence%of%neurotransmitter,%the%ion%channel%is%normally%
closed
When%neurotransmitter%binds%to%extracellular% sites%on%the%receptor,%
it%induces%a%conformational%change%in%the%receptor%protein%that%
opens%the%channel%to%pass%ions
The%resulting%changes%in%membrane%potential%is%considered
Excitatory:%membrane%potential%rises%toward%threshold
§
Inhibitory:%membrane%potential%is%lowered%from%threshold
§
Excitatory%Postsynaptic%Potential
Na+%passes%through%ion%channels
§
Depolarization%occurs
§
Inhibitory%Postsynaptic%Potential
Cl-passes%through%ion%channels
§
Dendrites%use%passive%conduction%to%transmit%PSPs%to%the%soma%(cell%body)%
and%axon%initial%segment
If%the%EPSP%is%large%enough%when%it%gets%to%the%axon%initial%segment,%an%
action%potential%results
IPSPs%resist%membrane%depolarization
Synaptic%summation%is%usually%required%to%generate%an%action%potential
Types%of%Synaptic%Summation
Spatial
§
Simultaneous%input%from%multiple%synapses%sum%to%generate%a%
larger%EPSP
Temporal
§
Rapid%succession%of%EPSPs%at%the%same%synapse%sum%to%
depolarize%the%neuron%more%than%a%single%EPSP%would%have
Summary%of%Chemical%Synaptic%Transmission
Neurotransmitter%release
Receptor%binding
Ion%channels%open%or%close
Conductance%change%causes%current%flow
Postsynaptic%potential%changes
Postsynaptic%cells%excited%or%inhibited
Summation%determines%whether%or%not%an%action%potential%occurs
Toxins%blocking%synaptic%transmission:%tetrodotoxin
Na+%channel%blocker%-blocks%action%potentials
Found%in%a%variety%of%marine%and%terrestrial%animals
Causes%paralysis,%loss%of%sensation,%cardiac%arrhythmias
Death%normally%due%to%respiratory%depression
Toxins%blocking%synaptic%transmission
Botulism
§
Paralysis%of%peripheral%neuromuscular%junctions,%including%
diaphragm%and%other%respiratory%muscles
Tetanus%("lockjaw")
§
Blocks%inhibitory%transmission%from%interneurons%in%spinal%cord%
producing%hyper%excitation%of%skeletal%muscle
Impair%vesicular%release%with%primary%effects%at%different%synapses
Electrical% Synapses%Do%Exist:%Gap%Junctions
Gap%junctions%are%made%of%paired%channels%called%connexons
One%channel%of%the%pair%is%in%the%presynaptic%neuron%-the%other%in%
the%postsynaptic%neuron
Connexon%pore%is%much%larger%than%the%pore%of%ion%channels
A%variety%of%substances%can%diffuse%between%the%cytoplasm%of%the%
pre-and%postsynaptic%neurons,%e.g.%ions,%ATP,%sugars,%"second%
messengers"
Electrical% Synapses:%bidirectional
Allow%ionic%current%to%flow%passively%from%one%neuron%to%another
Transmission%is%extraordinarily%fast
Fulfill%critical%roles%at%"escape"%synapses%and%in%synchronizing%activity%
in%networks%of%neurons
Not%all%synapses%are%from%axons%to%dendrites
Axodendritic
Axosomatic
Axoaxonic%
Synaptic%Circuits
Convergence:%many%signals%lead%to%one%neuron
Divergence:%one%signal%splits%into%many
Serial%processing
Parallel%processing
Synaptic%Circuits:%"Canonical"%excitatory%circuits
Feeds%forward
§Sequential
Feedback
§Loop
§Recurrent%excitation
Different%Ways%that%Feedback%and%Inhibition%can%occur
Feedback%can%trigger%inhibition
Presynaptic%Inhibition
§Turns%off%before%the%signal%even%gets%to%the%postsynaptic%
neuron
§Stops%the%pre-synapse%before%even%starting
Feedforward%Inhibition
§The%signal%goes%through,%then%the%channel%switches%off
Recurrent%Inhibition
§Axon-axon
§Shoots%out%inhibition%trigger%repeatedly%and%might%prevent%
axon%from%sending%off%an%action%potential
Complex%functionality%arises%quickly%from%combining%excitatory%and%
inhibitory%synapses
The%Neuron%Doctrine%and%Theory%of%Dynamic%Polarization%Revisited
Electrical% synapses
Dendrodendritic,%axodendritic,%axoaxonic%synapses
§Violate%the%theory%of%dynamic%polarization
§Leave%open%the%possibility%that%for%certain%types%of%synaptic%
signaling%in%certain%parts%of%the%brain%leave%out%the%soma%and%
integration%of%signals%altogether
10/16%Lecture
Monday,%October%16,%2017 4:05%PM
You're Reading a Preview

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