Complexities of Long-Term Potentiation

From Mechanisms of Memory by J. David Sweatt, Ph.D.

Glu

Reuptake

Retrograde Signal

Presynaptic = Altered•Neurotransmitter amount in vesicles•Number of vesicles released•Kinetics of release•Glutamate reuptake•Probability of vesicle fusion

Postsynaptic = Altered•Number of AMPA receptors•Insertion of AMPA receptors•Ion flow through AMPA channels•Membrane electrical properties

Additional possibilities include changes in number of total synaptic connections between two cells

Membrane Properties

Release

Binding

Potential Sites of Synaptic Modification in LTP

A B

E-S Potentiation in area CA1

Data courtesy of Erik Roberson

GABAergic Neuron

CA1 Axon

Schaffer Collaterals

Cl-

GABA

Diminished Cl- channel function produces increased

excitability

-

+

GABA-ergic interneuron model of E-S Potentiation

High FrequencyStimulation

Mem

bran

e po

tent

ial (

mV

)

-70

Time

Threshold for triggeringan action potential

Low FrequencyStimulation

Temporal integration in LTP induction

3

6

9

12

15

18

21

24

27

30

Time (sec)

3

6

9

12

15

18

21

24

27

30

Time (sec)

Theta Frequency StimulationC5-Hz

200

msec

200

msec

200

msec

200

msec…200

msec

• 5-Hz frequency for 30 sec• 150 total pulses

A

fEP

SP

slo

pe

(% o

f b

asel

ine)

Time(min)

-20 0 20 40 60

75

100

125

150

175

200

Po

pu

lati

on

Sp

ike

Am

pli

tud

e:E

PS

P s

lop

e(N

orm

aliz

ed)

D

Time during TFS(sec)

0 10 20 30

0

1

2

3

4

5

Dual Recording

Stratum Pyramidale

Stratum Radiatum

2 mV

5 msec

B

Theta Frequency Stimulation

Data and figure courtesy of Joel Selcher

GABAergic Neuron

CA1 Axon

Schaffer Collaterals

-

+

GABA

GABA-b receptor

-

Negative feedback onto presynaptic GABA-b receptors causes decrease in

GABA release

GABA-b receptors in temporal integration with TBS

-30 0 30 60 90 120 150 180

50

100

150

200

250

-30 0 30 60 90 120 150 180

50

100

150

200

250

EP

SP

Slo

pe (

Per

cent

of

Bas

elin

e)

Time (minutes)

Immediate, Early and Late LTP

Roberson, English and Sweatt (1996) Learn. Mem. 3:1-24

INDUCTION BLOCKED

EXPRESSION BLOCKED

MAINTENANCE BLOCKED

PERIOD OF DRUG TREATMENT

time

tetanus

EPSP

Induction, Maintenance and Expression of LTP

I-LTP maintenance Expression

E-LTP maintenance

L-LTP maintenance

Expression

Expression

Induction

Induction

Induction

Mechanisms of Induction, Maintenance and Expression

A BmCD8

Dis

tal

Dendrites with Spines

Courtesy of Liqun Lou, Stanford University Courtesy of E. Korkotian, The Weismann Institute

PKC inhibitor

Cell Body

Injection of PKC inhibitor

SignalSignal

Diffusible Messengers (i.e. NO, O2

-, AA)

Physical Coupling(i.e. Integrins)

Candidate Retrograde Signaling Molecules

Ba

ck p

rop

ag

atin

gA

ctio

n P

ote

ntia

l

De

po

lariz

atio

n

Silent Synapse

NMDA Receptor

Vesicle

AMPA Receptor

Silent Synapses

Alternative Mechanisms for LTP

Renger, Egles, and Liu (2001) Neuron 29:469-484.

Depotentiation and LTDA

B

C

Lee et al. (2000) Nature 405:955-959.

A B C

Modulation of LTP induction

Thomas, Moody, Makhinson and O’Dell (1996) Neuron 17:475-482.

Johnston, Hoffman, Colbert, and Magee (1999) Curr. Opin. Neurobiol. 9:288-292.

Gottschalk, Pozzp-Miller and Figurov (1998) J. Neurosci. 18:6830-6839

LTP Outside the Hippocampus

Shafe et al. J. Neurosci. 20:8177-8187.

The World’s “Deadliest” Marine Animal

BOX Jellyfish

Sea Wasp Species - Chironex Fleckeri

Synonyms - Box Jellyfish, Fire Medusa, Indringa.

Box Jellyfish projects into pedaliums, each of which may contain up to as many as fifteen tentacles each 3 metres in length

For mobility, the Box Jellyfish contracts with a jet-like motion, shooting itself along up to speeds of 4 knots.

It is presumed to have “eyes” connected to a nerve ring and the creature can take evasive action or move towards its prey.

http://www.dunder.webcentral.com.au/vaarallinen/meri_mus03.htm

http://www.dunder.webcentral.com.au/vaarallinen/meri_mus03.htm

Nematocyst(400X)

~4000/animal

The World’s Deadliest Marine Animal