Postsynaptic mechanisms

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Postsynaptic mechanisms
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Postsynaptic mechanisms
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Intracellular recordings
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Ionic basis of synaptic currents
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Synaptic inhibition

• A synaptic potential is considered inhibitory if
  it reduces the probability of firing an action
  potential in a neuron.
• Ionic basis of synaptic inhibition. Fast
  synaptic inhibition is mediated by Cl- ions
  permeating the glycine or GABAA receptor.
  Synaptic inhibition is attained by
  hyperpolarization cell i.e. making it more
  negative. This is accomplished by opening
  chloride channels, which results in inward flow
  of negatively charged chloride ions down their
  concentration gradient

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Synaptic inhibition
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Synaptic inhibition

• A synaptic potential can be depolarizing and yet
  be inhibitory. Depolarizing synaptic potentials
  can inhibit neurons if the ECl- is more
  hyperpolarized (negative) than the action
  potential threshold.
• Shunting inhibition Opening of chloride
  channels increases membrane conductance i.e.
  reduces membrane resistance. Based on ohms law
  (VIR), it takes more current (I) to change
  membrane potential (V) when resistance is lower.
• Inhibitory neurotransmitters can mediate
  excitation if ECl- is more depolarized than
  threshold and shunting inhibition is overcome.

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Synaptic kinetics

• Based on Katzs work on neuromuscular junction
  studying miniature end plate potentials,
  typically we study miniature synaptic currents to
  understand kinetics of synaptic currents.
• Miniature synaptic currents are recorded in the
  presence of tetrodotoxin to block action
  potentials in the presynaptic terminals.
  Neurotransmitter released due to spontaneous
  fusion of neurotransmitter filled vesicles
  activates receptors on postsynaptic membrane,
  resulting in mEPSCs or mIPSCs. In the example
  below synaptic currents recorded from a neuron
  before (A) and after application of TTX are
  displayed.

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Generic synapse
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Kinetics of synaptic response
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Kinetics of synaptic response

• Study of mechanisms that shape the synaptic
  current is referred to as synaptic kinetics. Why
  is it important to understand synaptic kinetics?
• The simplest (minimal) model used to understand
  factors that shape synaptic currents ) rise time,
  amplitude and decay is described below.

k1
T R
?
T R
T R
k2
?
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Kinetics of synaptic response
Factors determining the rise time of the synaptic
current 1) concentration of the
neurotransmitter released (T), k1 the
neurotransmitter receptor binding rate, b is
probability of channel opening when it is closed
and ? is probability that it closes from an open
state. . The values of ? and ? are determined by
single channel recordings.
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Kinetics of synaptic response

• Amplitude of a synaptic event is determined by
  the amount of neurotransmitter packaged in a
  single vesicle or the number of receptors present
  on the postsynaptic membrane. Exercise Design
  experiments to determine which of the two
  determine mIPSC (quantal size) at central
  synapses.
• The rate of removal of the neurotransmitter by
  diffusion, degradation, reuptake and the kinetic
  properties of the receptor (binding and gating)
  potentially shape decay of the miniature synaptic
  events. Exercise Design experiments to
  determine which of these factors
  (neurotransmitter concentration or receptor
  properties) play more important role in shaping
  the decay of synaptic currents?

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Summation

• Both temporal and spatial summation are non
  linear. Why?

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EPSCs
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EPSCs
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IPSCs
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Metabotropic and ionotropic receptors
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Silent synapses

• Types of silent synapses
• Presynaptic terminal present without any
  postsynaptic specialization.
• At an excitatory synapse where pre and
  postsynaptic elements are present but post
  synaptic element has only NMDA receptors.
• Branch point failures in transmission of action
  potentials down axons result in silent synapses.

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Extrasynaptic receptors

• AMPA receptors present in the extrasynaptic
  membrane move into synapses to mediate LTP.
• Extrasynaptic GABA receptor mediate tonic
  inhbition.