LECTURE 9: INTEGRATION OF SYNAPTIC INPUTS Ionotropic Receptors

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LECTURE 9 INTEGRATION OF SYNAPTIC INPUTS
(Ionotropic Receptors)
REQUIRED READING Kandel text, Chapter 12
At neuromuscular synapse, single axonal action
potential generates a muscle action
potential. The large arborized endplate contains
500,000 acetylcholine receptors generating 500
nA IEPSP sufficient to depolarize muscle past
threshold. Individual neuron-to-neuron synapses
are much smaller and do not generate sufficient
IEPSP to trigger action potential in postsynaptic
cell. Neuronal excitation requires
near-simultaneous inputs from multiple excitatory
synapses. E.g., a motor neuron will need 20-30
excitatory inputs to give EPSP beyond
threshold. Neurons also have synapses which
mediate inhibitory postsynaptic potentials
(IPSPs). IPSPs oppose depolarization generated by
EPSPs. Neurons continuously integrate inhibitory
and excitatory synaptic inputs to
determine whether to fire action potentials and
with what frequency.
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THE IPSP DETECTED IN MOTOR NEURON BY INPUT FROM
INTERNEURON
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TWO FUNCTIONS OF IPSPs

• IPSPs counteract EPSPs to reduce or abolish
  neural firing triggered
• by excitatory synaptic inputs.
• IPSPs can interfere with the rhythmic spontaneous
  firing of neurons.
• The pattern of inhibitory synaptic
  inputs sculpts the
• spontaneous periodic firing.

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EXCITATORY AND INHIBITORY SYNAPSES HAVE DIFFERENT
MORPHOLOGIES
Axo-axonic synapses do not directly generate
postsynaptic currents These synapses
mediate short- and long-term signaling
events that modulate how much neurotransmitter
is released by an action potential reaching its
terminus.
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MOST EXCITATORY SYNAPSES ELICIT EPSP WITH
REVERSAL POTENTIAL OF 0 mV
IONOTROPIC RECEPTOR
ION PERMEABILITY
NEUROTRANSMITTER
GLUTAMATE AMPA GluR Na, K GLUTAMATE
Kainate GluR Na, K GLUTAMATE NMDA
GluR Na, K, Ca ACETYLCHOLINE Nicotinic
AChR Na, K ATP ATP Receptor Na, K,
Ca SEROTONIN 5-HT3 Receptor Na, K
Excitatory reversal potential, EEPSP, is near 0
mV, due to permeability of receptor to
both sodium and potassium
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NMDA AND NON-NMDA RECEPTORS FUNCTION DIFFERENTLY
NMDA receptors open only when depolarization
precedes glutamate binding. Depolarization
releases Mg2 blocking particle from
ligand-binding site. NMDA receptors only open
with prolonged presynaptic activity. Calcium
entry through NMDARs induces signaling processes
that can modify synaptic behavior both short- and
long-term
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NMDA RECEPTORS CONDUCT LATE CURRENT AFTER
DEPOLARIZATION
Whole Cell Recordings in V-Clamp
Single Channel Recordings in V-Clamp
NMDA receptors open only when depolarization
precedes glutamate binding. Depolarization
release Mg2 blocking particle from
ligand-binding site. NMDA receptors only open
with prolonged presynaptic activity. Calcium
entry through NMDARs induces signaling processes
that can modify synaptic behavior both short- and
long-term
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MOST INHIBITORY SYNAPSES ELICIT IPSP WITH
REVERSAL POTENTIAL OF -60 mV
IONOTROPIC RECEPTOR
ION PERMEABILITY
NEUROTRANSMITTER
GABA GABAA Receptor Cl- Glycine
Glycine Receptor Cl-
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IPSP ACTS TO SHORT-CIRCUIT EPSP CURRENT AND BLOCK
DEPOLARIZATION
TWO WAYS TO THINK OF HOW IPSP CURRENTS INHIBIT
EXCITATION

• Goldmans equation shows that membrane potential
  is driven to a level
• determined by the weighted sum of
  each ionic Nernst potential weight
• by the relative permeability of each
  ion.
• Increasing Cl- or K permeability
• reduces the effect of
• excitatory Na current
• II. Inhibitory channels gate ions (usually
  Cl-) with Nernst (reversal) potential
• of -60 to -70 mV. Since this is
  about the same potential as that of leak
• channels, we can consider inhibitor
  channels as increasing the leak
• conductance. Since at the peak of
  an EPSP, IEPSP(in) Ileak(out),
• Ohms law says DVEPSP IEPSP(in)
  / gleak. The larger the leak conductance
• the smaller the depolarization
  induced by excitatory inward currents.

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INTEGRATION OF MULTIPLE SYNAPTIC INPUTS
DETERMINED BY CELL ARCHITECTURE, ACTIVE
DENDRITIC CURRENTS, AND LEAK CURRENTS
Time constant of an EPSP determined by leak
conductance. If leak conductance is low, EPSP
persists well after IEPSP current ends (long time
constant). A second IEPSP can induce
further depolarization than did the first. This
is called TEMPORAL SUMMATION If leak
conductance is high, EPSP is finished before a
second IEPSP , so there is no temporal summation
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INTEGRATION OF MULTIPLE SYNAPTIC INPUTS
DETERMINED BY CELL ARCHITECTURE, ACTIVE
DENDRITIC CURRENTS, AND LEAK CURRENTS
Length constant of an EPSP determined by ratio
of axial conductance to leak conductance
I.e., by the cable properties of the
dendrite The greater the ratio of gdendrite
to gleak, the less an EPSP diminishes over
distance I.e., the bigger the length
constant EPSP with bigger length constant can
more readily undergo spatial summation with the
EPSP at another synapse
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INTEGRATION OF MULTIPLE SYNAPTIC INPUTS
DETERMINED BY CELL ARCHITECTURE, ACTIVE
DENDRITIC CURRENTS, AND LEAK CURRENTS
Axosomatic inhibitory synapse exerts a more
powerful inhibitory effect on excitation than
does an axodendritic inhibitory
synapse. Axosomatic inhibitory currents are
shunts preventing dendritic EPSPs from
propagating past to reach the trigger zone.
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INTEGRATION OF MULTIPLE SYNAPTIC INPUTS
DETERMINED BY CELL ARCHITECTURE, ACTIVE
DENDRITIC CURRENTS, AND LEAK CURRENTS
In large neurons with long, extensively arborized
dendrites, currents from dendritic voltage-gated
calcium channels (VGCCs) can boost distant
dendritic EPSPs towards the soma. The density of
VGCCs in proximal dendritic trunk and soma are
much lower, so active propagation does not
proceed across soma to sodium channel trigger
zone. Temporal and spatial summation of
excitatory inputs are still required to induce
the axonal action potential.
EPSP in DISTAL DENDRITE
CALCIUM ACTION POTENTIAL DOWN DENDRITE
SUBTHRESHOLD DEPOLARIZATION in PROXIMAL DENDRITE
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SUBUNIT STRUCTURES OF LIGAND GATED IONOTROPIC
RECEPTORS
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IMPERMEABILITY OF AMPA RECEPTORS TO CALCIUM
GENERATED BY RNA EDITING
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NEXT LECTURE Metabotropic Receptors READING
KANDEL text, Chapter 13