8/8/2019 Complexities of Long-Term ion

1/18

8/8/2019 Complexities of Long-Term ion

2/18

Glu

Reuptake

Retrograde Signal

Presynaptic= AlteredNeurotransmitter amount in vesiclesNumber of vesicles releasedKinetics of release

Glutamate reuptakeProbability of vesicle fusion

Postsynaptic= AlteredNumber of AMPA receptorsInsertion of AMPA receptorsIon 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

8/8/2019 Complexities of Long-Term ion

3/18

8/8/2019 Complexities of Long-Term ion

4/18

GABAergic Neuron

CA1 Axon

Schaffer Collaterals

Cl-

GABA

Diminished Cl- channel

function produces increased

excitability

-

+

GABA-ergic interneuron model of E-S Potentiation

8/8/2019 Complexities of Long-Term ion

5/18

High Frequency

Stimulation

Membra

nepo

t ential(mV)

-70

Time

Threshold for triggering

an action potential

Low Frequency

Stimulation

Temporal integration in LTP induction

8/8/2019 Complexities of Long-Term ion

6/18

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

200msec

5-Hz frequency for 30 sec 150 total pulses

A

fEPSP

slope

(%

ofbaselin

e)

Time(min)

-20 0 20 40 60

75

100

125

150

175

200

PopulationSpike A

mplitud

e:

EPSPslo p

e

(Normalized)

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

8/8/2019 Complexities of Long-Term ion

7/18

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

8/8/2019 Complexities of Long-Term ion

8/18

-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

EPSPSlope(P

erc

entofBase

line)

Time (minutes)

Immediate, Early and Late LTP

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

8/8/2019 Complexities of Long-Term ion

9/18

INDUCTION BLOCKED

EXPRESSION BLOCKED

MAINTENANCE BLOCKED

PERIOD OF DRUG TREATMENT

time

tetanus

EPSP

Induction, Maintenance and Expression of LTP

8/8/2019 Complexities of Long-Term ion

10/18

I-LTP maintenance Expression

E-LTP maintenance

L-LTP maintenance

Expression

Expression

Induction

Induction

Induction

Mechanisms of Induction, Maintenance and Expression

8/8/2019 Complexities of Long-Term ion

11/18

A BmCD8

Dista

l

Dendrites with Spines

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

8/8/2019 Complexities of Long-Term ion

12/18

PKC inhibitor

Cell Body

Injection of PKC inhibitor

8/8/2019 Complexities of Long-Term ion

13/18

SignalSignal

Diffusible Messengers

(i.e. NO, O2-

, AA)

Physical Coupling(i.e. Integrins)

Candidate Retrograde Signaling Molecules

8/8/2019 Complexities of Long-Term ion

14/18

B

ackpropagating

A

ctionPote

ntial

Depolariza

tion

Silent Synapse

NMDA Receptor

Vesicle

AMPA Receptor

Silent Synapses

8/8/2019 Complexities of Long-Term ion

15/18

Alternative Mechanisms for LTP

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

D t ti ti d LTD

8/8/2019 Complexities of Long-Term ion

16/18

Depotentiation and LTD

A

B

C

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

8/8/2019 Complexities of Long-Term ion

17/18

A B C

Modulation of LTP induction

Thomas, Moody, Makhinson and ODell

(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

8/8/2019 Complexities of Long-Term ion

18/18

LTP Outside the Hippocampus

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