Download - Synaptic Hypothesis
-
8/12/2019 Synaptic Hypothesis
1/37
Strong claim:Synaptic plasticity is the only game in town.
Weak Claim:
Synaptic plasticity is a game in town.
-
8/12/2019 Synaptic Hypothesis
2/37
The cortex has ~109
neurons.
Each Neuron has up to 104
synapses
-
8/12/2019 Synaptic Hypothesis
3/37
-
8/12/2019 Synaptic Hypothesis
4/37
Central Hypothesis
Changes in synapses underlie the basis of
learning, memory and some aspects ofdevelopment.
What is the connection between these seemingly very
different phenomena?
Do we have experimental evidence for thishypothesis
A cellular correlate of Learning, memory-
receptive field plasticity
-
8/12/2019 Synaptic Hypothesis
5/37
Classical Conditioning Hebbs rule
When an axon in cell is near enough to excite cell Bandrepeatedly and persistently takes part in firing it, somegrowth process or metabolic change takes place in oneor both cells such that s efficacy in firing Bis increased
Ear
Tongue
Nose
B
D. O. Hebb (1949)
-
8/12/2019 Synaptic Hypothesis
6/37
Two examples of Machine learning based on
synaptic plasticity
1.The Perceptron (Rosenblatt 1962)
2. Associative memory
(We will talk about these next week)
-
8/12/2019 Synaptic Hypothesis
7/37
Synaptic plasticity evoked artificially
Examples of Long term potentiation (LTP)and long term depression (LTD).
LTP First demonstrated by Bliss and Lomo in
1973. Since then induced in many different ways,usually in slice.
LTD, robustly shown by Dudek and Bear in 1992,
in Hippocampal slice.
-
8/12/2019 Synaptic Hypothesis
8/37
Artificially induced synaptic plasticity.
Presynaptic rate-based induction
Bear et. al. 94
-
8/12/2019 Synaptic Hypothesis
9/37
Feldman, 2000
Depolarization based induction
-
8/12/2019 Synaptic Hypothesis
10/37
Spike timing dependent plasticity
Markram et. al. 1997
-
8/12/2019 Synaptic Hypothesis
11/37
But how do we know that synaptic
plasticity as observed on the cellular level
has any connection to learning and memory?
What types of criterions can we use to answer
this question?
At this level we know much about the cellular
and molecular basis of synaptic plasticity.
-
8/12/2019 Synaptic Hypothesis
12/37
Assessment criterions for the synaptic hypothesis:
(From Martin and Morris 2002)
1. DETECTABILITY: If an animal displays memory
of some previous experience (or has learnt a new
task), a change in synaptic efficacy should be
detectable somewhere in its nervous system.
2. MIMICRY: If it were possible to induce the
appropriate pattern of synaptic weight changes
artificially, the animal should display apparentmemory for some past experience which did not
in practice occur.
-
8/12/2019 Synaptic Hypothesis
13/37
3. ANTEROGRADE ALTERATION: Interventions
that prevent the induction of synaptic weight
changes during a learning experience should impair
the animals memory of that experience (or prevent
the learning).
4. RETROGRADE ALTERATION: Interventions that
alter the spatial distribution of synaptic weight
changes induced by a prior learning experience
(see detectability) should alter the animals memoryof that experience (or alter the learning).
-
8/12/2019 Synaptic Hypothesis
14/37
Detectability
Example from Rioult-Pedotti - 1998
-
8/12/2019 Synaptic Hypothesis
15/37
Example: Inhibitory avoidance
Fast
Depends on Hippocampus
Whitlock et. al. 2006
-
8/12/2019 Synaptic Hypothesis
16/37
Occlusion of LTP in
trained hemisphere
More LTD in trained
hemisphere
(Riolt-Pedoti 2000)
-
8/12/2019 Synaptic Hypothesis
17/37
Mimicry: Generate a false memory, teach a
skill by directly altering the synaptic
connections.
This is the ultimate test, and at this point in
time it is science fiction.
-
8/12/2019 Synaptic Hypothesis
18/37
ANTEROGRADE ALTERATION:
Interventions that prevent the induction of synaptic
weight changes during a learning experienceshould impair the animals memory of that
experience (or prevent the learning).
This is the most common approach. It relieson utilizing the known properties of synaptic
plasticity as induced artificially.
-
8/12/2019 Synaptic Hypothesis
19/37
Example: Spatial learning is impaired by block of
NMDA receptors (Morris, 1989)
Morris water mazerat
platform
-
8/12/2019 Synaptic Hypothesis
20/37
-
8/12/2019 Synaptic Hypothesis
21/37
4. RETROGRADE ALTERATION: Interventions that
alter the spatial distribution of synaptic weight changes
induced by a prior learning experience should alter the
animals memory of that experience (or alter the
learning).
Lacuna memory control
http://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.movhttp://localhost/var/www/apps/conversion/tmp/scratch_8/EternalSunshineCropped.mov -
8/12/2019 Synaptic Hypothesis
22/37
Receptive field plasticity is a cellular
correlate of learning.
What is a receptive field?
First describedsomatosensory receptive
fields (Mountcastle)
Best known examplevisual receptive fields
-
8/12/2019 Synaptic Hypothesis
23/37
Visual Pathway
Area
17LGN
Visual Cortex
Retina
light electrical signals
Monocular
RadiallySymmetric
Binocular
OrientationSelective
Receptive fields are:
Receptive fields are:
-
8/12/2019 Synaptic Hypothesis
24/37
Left Right
Tuning curves
0 180 36090 270
RightLeft
-
8/12/2019 Synaptic Hypothesis
25/37
Tuning curves and receptive fields
A feed forward model of
orientation selective cells
in visual cortex.
(Hubel and Wiesel model
of simple cell)
-
8/12/2019 Synaptic Hypothesis
26/37
Receptive field plasticity is a correlate of learning
An imaginary example
Learning to discriminate between similar lines
G li ti f th i f RF d S l ti it
-
8/12/2019 Synaptic Hypothesis
27/37
Generalization of the meaning of RF and Selectivity
First described in somatosensory cortex (Mountcastle)
Retinal cell RFs
Simple cell RF in primary Visual cortex (VC)
Complex cell in VC
Motion selective cells in area MT
Selective cells in Auditory areas
Is there another form of representation?
Receptive field plasticity can be induced by
-
8/12/2019 Synaptic Hypothesis
28/37
Receptive field plasticity can be induced by
changes in the visual environment
BinocularDeprivation
Normal
Adult
Eye-opening angleangle
Eye-opening
Adult
-
8/12/2019 Synaptic Hypothesis
29/37
Monocular
DeprivationNormal
Left Right
%o
fcells
group group
angleangle
1 2 3 4 5 6 7
10
20
1 2 3 4 5 6 7
30
15
Right
Left
Rittenhouse et. al.
-
8/12/2019 Synaptic Hypothesis
30/37
Receptive field Plasticity
Ocular Dominance
Plasticity (Mioche and Singer, 89)
Synaptic plasticity in Visual
Cortex (Kirkwood and Bear, 94 )
Left Eye Right EyeStimulate Record
30150-15
50
100
150
200
HFS
Time fromonsetofLFS (min)
4530150-15-3050
75
100
125
150
1 Hz
-
8/12/2019 Synaptic Hypothesis
31/37
Evidence that Ocular Dominance plasticity depends
on synaptic plasticity.
Bear et. al. 1990
-
8/12/2019 Synaptic Hypothesis
32/37
Similar experiment using Antisense for NR1 in Ferrets
Roberts et. al. 1998
-
8/12/2019 Synaptic Hypothesis
33/37
Blocking NMDAR
with Antisense
prevents the
development of
orientation selectivity
in Ferrets .
Ramoa et. al. 2001
-
8/12/2019 Synaptic Hypothesis
34/37
Heynen et. al. 2003
-
8/12/2019 Synaptic Hypothesis
35/37
Heynen et. al. 2003
LTD is the basis of Rat Ocular Dominance plasticity
-
8/12/2019 Synaptic Hypothesis
36/37
-
8/12/2019 Synaptic Hypothesis
37/37