Transcript A. Normal OD development - Molecular and Cell Biology

Activity-dependent
Development (2)
Hebb’s hypothesis
Hebbian plasticity in visual
system
Cellular mechanism of Hebbian
plasticity
1
Donald Hebb (1949)
When an axon of cell 1 is
near enough to excite a cell 2
and repeatedly and
persistently takes part in
firing it, some growth
process or metabolic change
takes place in one or both
cells such that 1's efficacy, as
one of the cells firing 2, is
increased.
Common interpretation:
“Cells that fire together wire
together”
Other people also made the following extension:
“neurons out of synch lose the
link”
Hebb’s rule has been a central hypothesis
guiding the studies of learning, memory,
and their cellular basis in the past several
decades
2
A property of Hebbian
synapse
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Hebb’s rule and OD
development
A. Normal OD development
Small differences in either the activity level or the initial
strength causes the postsynaptic cell activity to be more
similar (correlated) to the activity of the more
active/strong input. This input will be strengthened and
will win the competition.
left
cortical cell
in layer 4
right
4
B. Monocular deprivation
Deprived eye input is uncorrelated with cortical cell activity,
and will lose the competition
left
cortical cell
in layer 4
right
(MD)
C. Binocular deprivation
Similar to normal development. The outcome of
competition is determined by small differences in initial
input strengths or spontaneous activity levels of the two
inputs.
5
D. TTX, block all action potentials
Both eye inputs correlated with cortical cell, both stay
left
cortical cell
in layer 4
right
6
But, each layer 4 cortical neuron receives
inputs from many LGN axons representing
the same eye, why don’t these axons
compete with each other?
If two presynaptic cells are correlated with
each other, they do not compete!
Neighboring inputs representing the same
eye are believed to be highly correlated.
left
cortical cell
in layer 4
right
7
Further tests of Hebb’s rule in OD
development
 If you force inputs from the two eyes to be
correlated (synchronous stimulation), you can prevent
competition and OD segregation
If you make the inputs from the two eyes even less
correlated (asynchronous stimulation or strabismus),
you enhance competition and OD segregation (there
will be very few binocular cells in V1)
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Problem: OD exists to some extent
before eye opening
• Normal visual input may not be necessary
for the initial formation, but required for
fine tuning and maintenance of visual
circuit
• Initial OD development may depend on
spontaneous activity (e.g., retinal waves,
correlated between neighboring RGC, but
uncorrelated between the two eyes)
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OD in 3-eyed frog
(Constantine-Paton and Law)
A. normal frog
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B. three-eyed frog
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Molecular mechanism of Hebbian plasticity
1. NMDA receptor - coincidence detector
- ligand dependent (requires binding of Glu)
- voltage dependent (requires depolarization of the postsynaptic
cell to remove Mg2+ from the channel pore)
Pre and post fires asynchronously
Pre and post fires synchronously
presynaptic
presynaptic
Glu
Glu
Na+
Na+
Ca2+
Na+
Ca2+
Mg2+
NMDAR
Na+
Mg2+
NMDAR
Ca2+
postsynaptic
resting membrane
potential
postsynaptic
depolarization
trigger LTP, strengthen synapse
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Molecular mechanism of OD plasticity
1. NMDA receptor
-- Block NMDA receptor, prevent the segregation of OD columns
in three-eyed frog
A. Normal development
B. NMDA receptor blockade
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Molecular mechanism of OD plasticity
2. Neurotrophins
Criteria for neurotrophins to function as molecular
signals in synaptic plasticity:
1) expressed in the right places and at the right times
2) expression and secretion are activity-dependent
3) regulate aspects of neuronal function
4) For competitive plasticity, the amount of
neurotrophins should be limited
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Molecular mechanism of cortical plasticity
2. Neurotrophins
Development of OD
- target neuron depolarized, releases neurotrophin
- neurotrophin is taken up by the presynaptic axon
- promotes long-term growth and stabilization of the input.
from L eye
from R eye
pre-
postAxons from R eye
- relatively stronger
- cause larger depolarization in postsynaptic neuron
- larger amounts of neurotrophin release by postsynaptic neuron
- stabilize the input
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Molecular mechanism of cortical plasticity
2. Neurotrophins
Development of OD
- infusion of BDNF or NT-4/5, disrupt OD columns
A Normal
Layer 4
B NGF or NT-3 administration
NGF
no effect
NT-3
Layer 4
C NT-4/5 or BDNF administration
BDNF
NT-4/5
Layer 4
Disrupt
formation of
OD column
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Source of activity during OD development
1. Before eye-opening (before birth)
- spontaneous retinal wave
2. After eye-opening
- visually driven activity
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