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

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LECTURE 9: INTEGRATION OF SYNAPTIC INPUTS (Ionotropic Receptors)

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Lecture 9 integration of synaptic inputs ionotropic receptors

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 nAIEPSPsufficient 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.


Lecture 9 integration of synaptic inputs ionotropic receptors

THE IPSP DETECTED IN MOTOR NEURON BY INPUT FROM INTERNEURON


Lecture 9 integration of synaptic inputs ionotropic receptors

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.


Lecture 9 integration of synaptic inputs ionotropic receptors

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.


Lecture 9 integration of synaptic inputs ionotropic receptors

MOST EXCITATORY SYNAPSES ELICIT EPSP WITH REVERSAL POTENTIAL OF 0 mV

IONOTROPIC

RECEPTOR

ION

PERMEABILITY

NEUROTRANSMITTER

GLUTAMATE AMPA GluRNa+, K+

GLUTAMATE Kainate GluRNa+, K+

GLUTAMATE NMDA GluRNa+, K+, Ca++

ACETYLCHOLINENicotinic AChRNa+, K+

ATP ATP ReceptorNa+, K+, Ca++

SEROTONIN5-HT3 ReceptorNa+, K+

Excitatory reversal potential,

EEPSP,

is near 0 mV,

due to permeability of

receptor to both

sodium and potassium


Lecture 9 integration of synaptic inputs ionotropic receptors

NMDA AND NON-NMDA RECEPTORS FUNCTION DIFFERENTLY

NMDA receptors open only when depolarization precedes glutamate binding.

Depolarization releases Mg+2 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


Lecture 9 integration of synaptic inputs ionotropic receptors

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 Mg+2 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


Lecture 9 integration of synaptic inputs ionotropic receptors

MOST INHIBITORY SYNAPSES ELICIT IPSP WITH REVERSAL POTENTIAL OF -60 mV

IONOTROPIC

RECEPTOR

ION

PERMEABILITY

NEUROTRANSMITTER

GABA GABAA Receptor Cl-

Glycine Glycine Receptor Cl-


Lecture 9 integration of synaptic inputs ionotropic receptors

PKEK + PNaENa + PClECl

Vm =

PK + PNa + PCl

IPSP ACTS TO SHORT-CIRCUIT EPSP CURRENT AND BLOCK DEPOLARIZATION

TWO WAYS TO THINK OF HOW IPSP CURRENTS INHIBIT EXCITATION

Goldman’s 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),

Ohm’s law says DVEPSP = IEPSP(in) / gleak. The larger the leak conductance

the smaller the depolarization induced by excitatory inward currents.


Lecture 9 integration of synaptic inputs ionotropic receptors

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


Lecture 9 integration of synaptic inputs ionotropic receptors

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


Lecture 9 integration of synaptic inputs ionotropic receptors

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.


Lecture 9 integration of synaptic inputs ionotropic receptors

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


Lecture 9 integration of synaptic inputs ionotropic receptors

SUBUNIT STRUCTURES OF LIGAND GATED IONOTROPIC RECEPTORS


Lecture 9 integration of synaptic inputs ionotropic receptors

IMPERMEABILITY OF AMPA RECEPTORS TO CALCIUM GENERATED

BY RNA EDITING


Lecture 9 integration of synaptic inputs ionotropic receptors

NEXT LECTURE: Metabotropic Receptors

READING: KANDEL text, Chapter 13


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