Neuronal Plasticity

BySyed Mujtaba Hasnain Nadir

Mubarak Raza Wagha

What is neuronal plasticity?

Plasticity is the quality of being ‘plastic’ or formative.

Neuronal plasticity refers to the ability of the brain to change and adapt itself as a result of

one’s experience.

Applications of Neuronal Plasticity

• ‘Learning new things’• ‘Making new memories’• ‘Rewiring circuits’

Types of Long-term Memory

The NS is a series of connections

• Birth = 100 billion neurons

• 6 year old has twice as many synapses as an adult

• By late adolescence, synapses begin to disappear

http://www.eng.yale.edu/synapses.htm

Types of Neuroplasticity

Type Mechanism Duration

1. Enhancement of existing connectionsSynapse development Physiological ms-1 to hours

Synapse strengthening Biochemical hours to days

2. Formation of new connectionsUnmasking Physiological minutes to days

Sprouting Structural days to months

3. Formation of new cellsSelf-replication stem cell variable

Enhancement of existing connections

• Increased use of a synapse in existing pathways e.g. learning a new task

• Or alternative pathways following damage

• Cortical re-mapping (phantom limb)

Synapse development

Increased afferent input

New synapses evolve leading to increased excitation

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Synapse strengthening

Two point discrimination threshold in pianists index finger

R L

Ragert et al., 2004

Synaptic Strengthening

1. Facilitation (10-100 ms)

2. Augmentation (several seconds)

3. Potentiation (seconds to minutes)

Formation of new connections

• Unmasking of pre-existing pathways

• Sprouting of new pathways

Unmasking of silent synapses

Possible reasons why some synapses could be ‘silent’

• On distal dendrites• Inhibited by dominant pathways• Too little transmitter• Too few receptors• Don’t fire with other inputs

Unmasking – inhibition of subservient pathway by dominant pathway

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Subservient pathway

Parallel pathway; neurons with a comparable role

Dominant pathway

Unmasking

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Lesion to dominant pathway

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Subservient pathway is unmasked

Activity is continued

despite lesion

Sprouting

Cell body

AxonAP

Sprouting

lesion

INJURY

Nerve Growth Factor (NGF)

Sprouting

lesion

INJURY

NGF

Neurite induced to sprout by NGF

Sprouting

Cell is re-innervated from alternative

stimulus

Sprouting may be a means of recovery; it may also produce unwanted effects

Injury results in cell death

Neurogenesis• Replacing dying or damaged

neural cells with new ones

• New cells originate from stem cells

• Introduced stem cells are stimulated to produce neural cells by nerve growth factors (NGF)

Stem cell/www.stanford.edu/group/hopes/rltdsci/nplast

Cortical Re-Mapping

• People born deaf

Cortical Re-Mapping

• People born deaf– What happens?

Cortical Re-Mapping

• People born deaf– What happens?

Visual areas increase in size and “jobs”

Cortical Re-Mapping

• People born deaf– What happens?

Visual areas increase in size and “jobs”Auditory areas may be “taken over” for visual

function

Cortical Re-Mapping

• People born deaf– What happens?

Visual areas increase in size and “jobs”Auditory areas may be “taken over” for visual

function Improved attention to movement in the periphery

The Basis of Neuronal Plasticity

Hebb’s Rule :

“Neurons that fire together, wire together.””Neurons that fire apart, wire apart.”

From The Organization of Behavior by Donald Hebb, 1949:

• "When one cell repeatedly assists in firing another, the axon of the first cell develops synaptic knobs (or enlarges them if they already exist) in contact with the soma of the second cell."

• Hebb postulated that this behavior of synapses in neuronal networks would permit the networks to store memories.

Synaptic Strengthening

1. Facilitation (10-100 ms)

2. Augmentation (several seconds)

3. Potentiation (seconds to minutes)

Long Term Potentiation

In neuroscience, long-term potentiation (LTP) is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously.

Input specificity

• Once induced, LTP at one synapse does not spread to other synapses; rather LTP is input specific.

Cooperativity

• LTP can be induced by strong stimulation at one synapse

OR

• Weak stimulation at multiple synapses which together depolarize the post synaptic membrane to induce LTP

Hippocampus

Function:

• Consolidation of New Memories • Emotions• Navigation• Spatial Orientation

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

The post-synaptic region has both NMDA and AMPA receptors.

Glutamate first activates AMPA receptors. NMDA receptors do not respond until enough

AMPA receptors are stimulated and the neuron is partially depolarized.

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

NMDA receptors at rest have a magnesium ion (Mg2+) block on their calcium (Ca2+) channels.

After partial depolarization, the block is removed and the NMDA receptor allows Ca2+ to enter in response to glutamate.

Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 1)

Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 2)

Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 3)

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

The large Ca2+ influx activates certain protein kinases – enzymes that add phosphate groups to protein molecules.

One protein kinase is CaMKII – it affects AMPA receptors in several ways:

• Causes more AMPA receptors to be produced and inserted in the postsynaptic membrane.

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

CaMKII :• Moves existing nearby AMPA receptors into the active

synapse.• Increases conductance of Na+ and K+ ions in

membrane-bound receptors.These effects all increase the synaptic sensitivity to

glutamate.The activated protein kinases also trigger protein

synthesis

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

Strong stimulation of a postsynaptic cell releases a retrograde messenger that travels across the synapse and alters function in the presynaptic neuron.

More glutamate is released and the synapse is strengthened.

Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits

• Somatic intervention experiments – pharmacological treatments that block LTP impair learning.

• Behavioral intervention experiments – show that training an animal in a memory task can induce LTP.

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