Announcements Mid term room assignments posted to webpage A – HoS361 (Pavilion) Hoang –...

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Announcements• Mid term room assignments posted to

webpage

A – Ho S361 (Pavilion)

Hoang – Lischka S309

Lishingham - Ngui S143

Nguyen – Seguin S128

Sek – Zia H305

Lecture 02 S319

Lecture 01

A. Excitor B. Inhibitor

Record voltage

Simple case:

Vm

Threshold

Depolarizing excitatoryEPSP

hyperpolarizing inhibitoryIPSP

Vm

ThresholdBA

A+B=smaller

How to get hyperpolarizing potential?

• Neurotransmitter receptor is permeable to an ion whose Eion is more negative than resting membrane potential

• usually Cl- or K+

++ -80 mV

+60 mV

0 mV

Hyperpolarizing Synaptic Potential

K+

More complex case:

Vm

Depolarizing excitatory Depolarizing

ThresholdBA

Threshold

Vm

A+B=smaller

inhibitory

Why???

Reversal Potential

• Membrane potential at which there is no net synaptic current

eg. Frog NMJ

Control resting membrane potential

Current source

stimulus

-100

-50

0

+25

Measuring Reversal Potential

Reversal potential

Record membrane potential

Stimulate nerve

• Many neurotransmitter receptors are permeable to more than one ion– Non-selective

• The reversal potential depends on the equilibrium potential and permeability of each ion– It will usually be between the equilibrium

potential of the permeable ions

eg. Acetylcholine channel

• Permeable to both K+ and Na+

• For Frog muscle:• EK = -90 mV

• ENa = +60 mV

Vm=Erev

Erev>Vm>EK

VmEK

Na+

VmENa

K+

EK = -90 mV

Neurotransmitterreceptor

-90

ENa = +60 mV

-50

0

+25

Reversal potential

How can depolarizing potential be inhibitory?

• Excitatory synapses have a reversal potential more positive than threshold

• Inhibitory synapses have a reversal potential more negative than threshold

How can depolarizing potential be inhibitory?

Vm

ThresholdBA

Erev

Erev

Example: Cl- permeable receptorin a cell whose Vthresh >ECl- > Vm

Inhibition

• Channels of inhibitory synapses ‘short-circuit’ excitatory synapses

• Because neurotransmitter channels will drive the membrane potential toward their reversal potential

• Neurotransmitters and receptors

• Synaptic Integration

Types of Receptors1. Ligand-gated ion channels

• Neurotransmitter binding to receptor opens an ion channel

• Directly changes the membrane potential of the postsynaptic cell

• Also known as ‘fast’ synaptic transmission

2. G-Protein Coupled Receptors• Transmitter binds to receptor which activates

intracellular molecules• Can directly or indirectly change the membrane

potential• Also known as ‘slow’ synaptic transmission

Neurotransmitter Receptors

Ligand-gated ion channels

Acetylcholine(Nicotinic)

Excitatory

Glutamate(AMPA, NMDA)

Excitatory

Serotonin(5-HT3)

Excitatory

GABAA Inhibitory

Glycine Inhibitory

Neurotransmitter Receptors

G-Protein coupled receptors

Acetylcholine(muscarinic)

Usually excitatory

Glutamate(metabotropic)

Variable effects

Serotonin(5-HT1-7)

Variable effects

GABABinhibitory

Same neurotransmitter, different receptors

Activate intracellular molecules

Open or close ion channeldirect effect

G-protein coupled receptor

Regulate other cellular functionseg gene expression

GTPGDP

receptor

G-proteins

indirect effect

What happens to neurotransmitter after it is secreted?

• Acetylcholine– Broken down by Acetylcholinesterase into

Choline and Acetate– Choline transported back into nerve terminal

and resynthesized into Acetylcholine

• Glutamate– Transported into glia or the nerve terminal

and converted to glutamine

• Serotonin– A neurotransmitter used in the emotional

centres of the brain

– Prozac is a drug that inhibits the reuptake of serotonin

– Therefore, Prozac makes serotonin remain in synaptic cleft longer

Synaptic Integration

The sum of all excitatory and inhibitory inputs to a cell.

1. Spatial Summation

2. Temporal Summation

Spatial Summation• The addition of several inputs onto one

cellA B

B

A

A+B

B

A

A+B

Temporal Summation

AStim once

Stim twice

Stim twice

Synaptic Integration

Soma and dendritesSynaptic inputs Axon Hillock

Passive current flow

Above threshold?

Yes No

Action Potential Passive CurrentDecays to zero

Summation

Conducts down axon

Summary

• Excitation and inhibition in relation to the reversal potential

• Fate of neurotransmitters after release

• Types of transmitters and their receptors

• Synaptic integration leading to action potentials