Let us assume that repetition tends to induce lastingcellular changes... When an axon of cell A is near enoughto excite a cell B, some growth or metabolic change takesplace such that A's efficiency is increased.
Donald Hebb, 1949
The problem which philosophers have set themselves is thatof ascertaining, between thoughts which appear to spoutone out of the other, the principles of connection wherebytheir peculiar succession or coexistance might be explained.
William James, 1892
dendritic spine
sprouting of new terminal bouton
smaller, thicker neck of dendriticspine: offers less electrical resistance
increased release ofneurotransmitter
more postsynaptic receptors,larger response to neurotransmitter
nucleus from egg
nucleus from sperm
insert deletor for ampareceptor subunit glur1
allow eggto divide
birth: only some offspringcarry the deletion
CA1 field
entorhinal cortex
stimulate axons
record from dentate gyrus
dentate gyrus
CA3 field
Blocks of 4 trials
0 2 4 6 8 10
Late
ncy
(sec
s)
0
10
20
30
40
50
60
70
80
WTGluR-A-/- GluR-A-/- **
X Data
0 1 2 3
Tim
e (p
erce
nta
ge)
0
10
20
30
40
50
60
Adjacent LeftTargetAdjacent RightOppositePlot 1 Zero
GluR-A-/-WT
start
finish
Reisel et al., Nature Neuroscience. 2002
Blocks
0 2 4 6 8 10 12 14
Co
rre
ct re
sp
on
se
(p
erc
en
tag
e)
40
50
60
70
80
90
100
WTGluR-A-/-
Blocks of 10 trials
0 1 2 3 4 5
Cor
rect
res
pons
es (
perc
enta
ge)
40
50
60
70
80
90
100
WTGluR-A-/-
Reisel et al., Nature Neuroscience. 2002
1 deletion of the glur1 gene disrupts plasticity
3 it is however involved in working memory
2 this type of plasticity is not involved in long term memory
Schmitt et al., Journal of Neuroscience, 2003
Schmitt et al., Journal of Neuroscience, 2003
Block
0 1 2 3 4 5 6 7
Esca
pe
la
ten
cy (
s)
0
10
20
30
40
50
60
70
80
WT lesionGluR-A-/- shamGluR-A-/- lesionWT sham
Blocks of 4 trials
0 2 4 6 8 10
Late
ncy
(sec
s)
0
10
20
30
40
50
60
70
80
WTGluR-A-/- GluR-A-/- **
Reisel et al., Nature Neuroscience. 2002
Blocks
0 2 4 6 8 10 12 14
Co
rre
ct re
sp
on
se
(p
erc
en
tag
e)
40
50
60
70
80
90
100
WTGluR-A-/-
Blocks
0 1 2 3 4 5
Pe
rce
nta
ge
co
rre
ct
30
40
50
60
70
80
90
WT lesion GluR-A-/- lesionWT shamGluR-A-/- sham
Reisel et al., Nature Neuroscience. 2002
10 seconds delay Response
time
GluR1 knockout mice are impaired on a delayed response task (DRL), with a delay of 15 seconds
GluR1 knockout mice show normal acquisition of a non-spatial delayed response task (DRL), with a delay of 10 seconds
Delayed Response Task (DRL): 10 vs. 15 seconds delays
Blocks
0 1 2 3 4 5
Perc
enta
ge c
orre
ct
0
10
20
30
40
50
60
70
WTGluR1 -/-
Blocks
0 1 2 3 4 5
Pe
rce
nta
ge
co
rre
ct
0
10
20
30
40
50
60
70
WTGluR1 -/-
Hopfield's terrain model of memory