Strong claim: Synaptic plasticity is the only game in town. Weak Claim: Synaptic plasticity is a game in town.

The cortex has ~109 neurons. Each Neuron has up to 104 synapses

Central Hypothesis Changes in synapses underlie the basis of learning, memory and some aspects of development.
What is the connection between these seemingly very different phenomena? Do we have experimental evidence for this hypothesis

A cellular correlate of Learning, memoryreceptive field plasticity

Classical Conditioning
Ear

Hebbs rule
A
Nose

B
Tongue

When an axon in cell A is near enough to excite cell B and repeatedly and persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that As efficacy in firing B is increased
D. O. Hebb (1949)

Two examples of Machine learning based on synaptic plasticity 1.The Perceptron (Rosenblatt 1962) 2. Associative memory (We will talk about these next week)

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.

Artificially induced synaptic plasticity.

Presynaptic rate-based induction

Bear et. al. 94

Depolarization based induction

Feldman, 2000

Spike timing dependent plasticity

Markram et. al. 1997

At this level we know much about the cellular and molecular basis of synaptic plasticity.

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?

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 apparent memory for some past experience which did not in practice occur.

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 memory of that experience (or alter the learning).

Detectability
Example from Rioult-Pedotti - 1998

Example: Inhibitory avoidance

Fast
Depends on Hippocampus

Whitlock et. al. 2006

Occlusion of LTP in trained hemisphere

More LTD in trained hemisphere

(Riolt-Pedoti 2000)

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.

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).
This is the most common approach. It relies on utilizing the known properties of synaptic plasticity as induced artificially.

Example: Spatial learning is impaired by block of NMDA receptors (Morris, 1989)

platform

Morris water maze

rat

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

Receptive field plasticity is a cellular correlate of learning. What is a receptive field?

First described somatosensory receptive fields (Mountcastle) Best known example visual receptive fields

Visual Pathway
Visual Cortex
Receptive fields are:

Binocular Orientation Selective Area 17

LGN
Receptive fields are:

Monocular Radially Symmetric Retina light electrical signals

Left

Right

Left

Right

Tuning curves

90

180

270

360

Tuning curves and receptive fields

A feed forward model of orientation selective cells in visual cortex. (Hubel and Wiesel model of simple cell)

Receptive field plasticity is a correlate of learning An imaginary example Learning to discriminate between similar lines

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 changes in the visual environment

Normal Binocular Deprivation

Adult Adult

Eye-opening angle

angle

Eye-opening

Normal

Monocular Deprivation

Left

Right

Right

Left

angle % of cells
20 30 15 10 1 2 3 4 5 6 7 1 2

angle

group

Rittenhouse et. al.

3 4

group

Receptive field Plasticity

Ocular Dominance Plasticity (Mioche and Singer, 89)
Left Eye Right Eye

Synaptic plasticity in Visual Cortex (Kirkwood and Bear, 94 )

S t im u l a t e R e c o rd

150 125 100 75 1 Hz 50 -3 0 -1 5 0 15 30 45

Ti m e f r o m o n s e t o f L F S ( m in )

200

150

100

HFS
50 -1 5 0 15 30

Evidence that Ocular Dominance plasticity depends on synaptic plasticity.

Bear et. al. 1990

Similar experiment using Antisense for NR1 in Ferrets

Roberts et. al. 1998

Blocking NMDAR with Antisense prevents the development of orientation selectivity in Ferrets .

Ramoa et. al. 2001

Heynen et. al. 2003

LTD is the basis of Rat Ocular Dominance plasticity

Heynen et. al. 2003

So what did we learn today?

What is the support for the claim that synaptic plasticity is the basis of learning and memory?