Post on 20-Jan-2016
description
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.
Nematocyst(400X)
~4000/animal
The World’s Deadliest Marine Animal