Download neuroplasticity 2016

Neuroplasticity
• Lundy-Ekman, Chapter 4
• Dr. Donald Allen
Outcomes
• Describe habituation and its role in therapy.
• Explain what is happening during long-term
potentiation.
• Describe the anatomical and metabolic
features of injury to the nervous system.
• Describe the anatomical changes that can
occur during the recovery from injury.
• Describe the effects of forced use on
recovery from an injury.
Plasticity
• What makes something plastic?
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Neuroplasticity
• Any change in the nervous system that is
not periodic
– Duration of more than a few seconds
– Combination of both flexibility and stability
Types of Neuroplasticity
• Habituation
• Learning and Memory
• Recovery from Injury
Habituation
• Considered by some to be the simplest form of
learning
• Decreased response to a repeated innocuous
stimulus
• Involves changes in neurotransmitter release
(strength of synaptic connections)
• Reversible
– Stop repeating the stimulus
– Change the stimulus
– Sensitizing stimulus
http://www.people.virginia.edu/~jyl8b/Percep/infant.html
How could you use habituation?
• Use of techniques and exercises to
decrease the neural response to a
stimulus
Learning and Memory
• More long-lasting, persistent
• Also involves changes in strength of
synaptic connections
• 3 Main types of learning and memory
Motor Memory
• AKA: Procedural
memory
• Learning a task
– Riding a bike
Verbal Memory
• Declarative memory
• Items that can be spoken or written
• Repetition?
Emotional Memory
• Not well understood
• Memory for associations of emotions with
specific places, people, etc.
Neurological mechanisms of
Learning and Memory
• Neuroimaging techniques
– Initial stages of motor learning
• Large and diffuse areas of the brain involved
– With repetition
• Decrease in number of brain regions which are
active
– Task learned
• Only small, distinct regions of the brain show
activity during performance of a task
Long-Term Memory
• Long-term memory requires the synthesis of
new proteins and growth of new synaptic
connections
– In animal studies, giving protein synthesis
inhibitors blocks the formation of new
memories
Long-term Potentiation
• Proposed mechanism to explain long-term
memory
• Occurs in hippocampus (part of temporal
lobe)
• Hippocampus is important for processing
verbal memory
– Bilateral damage to hippocampus results in an
inability to form new verbal memories
Studies on LTP
• Repetitive stimulation will increase the responses
to the stimulus
• Started with animal studies – slices of
hippocampus
– Treatment
• Single stimulus – measure response
• Repeated stimuli
• Single stimulus – measure response – now much
larger response
• http://users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/L/LTP.html
Requirements for LTP
• Cooperativity
• Associativity
• Specificity
Cooperativity
• There must be multiple excitatory inputs
into the hippocampal neuron that will
exhibit LTP
• The multiple inputs have an additive effect
• The individual inputs do not have to be
strong. Even weak inputs can show
potentiation is they occur in association
with strong inputs
Associativity
• Both the presynaptic fibers and the
postsynaptic cell must be activated together
– An action potential in the presynaptic axon
must produce an action potential in the
postsynaptic neurons
– I.e. The synapse must be effective
Specificity
• Only synapses that are associated with an
action potential in the postsynaptic neuron
will be potentiated.
Effects of LTP
• Involves
– Increases in synaptic activity
– Increased effectiveness of neuron firing
Role of non-neuronal cells in
LTP
• Astrocytes
– Change shape rapidly in response to stimulation
– Increase in astrocyte-neuron contacts in rats
raised in challenging environment compared to
standard conditions
Mechanism of LTP
• Conversion of ‘silent synapses’ into active
synapses
• Postsynaptic membrane is remodeled to form new
dendritic spines and synapses
Recovery from Injury
• What we see depends on what parts of the
neuron are injured
– Cell body
– Axon
Injury to cell body
• If severe, will kill the cell
– In general, dead neurons are not replaced
– However, changes in the remaining neurons can
promote recovery after the injury
Injury to Axon
• Will cause degenerative changes, but will
not necessarily kill the neuron
• If axon severed, the two ends will seal
• We now have a proximal section of the
axon, which is attached to the cell body, and
a distal section, which continues to the
presynaptic terminal
Distal section of axon
• This section is separated from the cell body
and will degenerate
– Wallerian degeneration
• Glial cells will clean up the degenerating
neurons. In the peripheral nervous system,
what kind of glial cells will these be?
• The postsynaptic cell will show some
degenerative changes (it has lost inputs)
– Trans-synaptic degeneration
– Some may die. It depends on the importance of
the lost inputs
Proximal section of axon
• Still attached to soma, so has the potential
to survive depending on what happens to
the neuron
– Central chromatolysis – dissolution of Nissl
substance in the cell body
– Cell body may die
Central Chromatolysis
Recovery After an Injury
• Recovery is affected by age at time of
injury
– Recovery decreases with age
– Children can have an entire cerebral
hemisphere removed and show little permanent
deficits
Regrowth of Axons after Injury
• Sprouting (page 72, Fig 4-4)
– Collateral sprouting
• Denervated target is reinnervated by branches of
intact axons
– Regenerative sprouting
• Target and axon both damaged
• Target dies
• Injured axon sends out collaterals to new targets
Functional Regeneration
• More prevalent in peripheral nervous
system
• Schwann cells make growth factors that
contribute to recovery of peripheral axons
– NGF- Nerve growth factor
• Recovery is better with a crush injury
compared to a cutting injury
• Growth is slow: 1 mm/day = 1 inch/month
CNS regeneration
• Little or no functional regeneration
– No Schwann cells producing NGF
– Oligodendrocytes inhibit growth of neurons
– Incomplete cleanup of cellular debris by
microglia
Potential problems during
regeneration
• Sprouting may innervate inappropriate
targets
– Motor neurons may innervate different muscles
• May produce unintentional movements
• Synkinesis
• These movements are usually short-lived, and the
individual relearns muscle control
– Can also see confusion of sensory modalities
Changes in synapses after injury
• Local edema and recovery of synaptic
effectiveness
• Denervation hypersensitivity
• Synaptic hypereffectiveness
• Unmasking of silent synapses
Effects of edema
• Local edema can occur after an injury
• The edema can put pressure on axons or cell
bodies
• Some synapses may become inactive
• Return of synaptic effectiveness
– As the edema resolves, the effectiveness of the
synapses can return
• What does this mean for therapists?
– Immediately after an injury, there can be a loss
of function
– Permanent or Temporary?
– As edema resolves, the patient may exhibit a
return of function
Denervation hypersensitivity
• Occurs when there is damage to presynaptic
terminals
• The postsynaptic cells lose all or some of
their synaptic inputs
• Neurons like to maintain a moderate level
of stimulation. Denervation removes this
stimulation.
• Postsynpatic neurons (and muscles) respond
by producing more receptors
– These new receptors will respond to
neurotransmitters that are released by adjacent
axons
Neuromuscular Junction and
Denervation
Synaptic hypereffectiveness
• Sometimes only some of the axon branches of a
neuron are damaged
• The presynaptic cell body still makes the usual
amount of neurotransmitter, but now the
neurotransmitter is distributed to less presynaptic
terminals
• Therefore, each terminal receives more
neurotransmitter, and more neurotransmitter is
released at each synapse
Unmasking of silent synapses
• Disinhibition of silent synapses
• Many synapses in the central nervous
system appear to be non-functional (silent)
• An injury to pathways in the brain can
unmask these synapses and they can
become functional
What chemicals are important for
these changes in synapses?
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NMDA receptors
Ca++ ions
Neurotrophins (growth factors)
Substance P
Nitric oxide
Changes in subtypes of sodium ion channels
Functional Reorganization of the
Cerebral Cortex
• When we look at somatosensory and motor
areas of the cortex, we find that specific
parts of the body can be mapped onto the
surface of the cerebral cortex.
• Determined by:
– Studies like Broca’s and Wernicke’s
– Recording which areas of the cortex show
electrical activity after sensory stimulation or
active muscle contraction
• Further studies using MRI have confirmed the
electrical studies
• Large areas of cortex represent the hands and face
(high number of sensory receptors and need for
controlled movements)
• For somatosensation, there are actually several
different maps that are parallel to each other
• General map for humans, but there will be
differences between individuals
Changes in the Somatotopic map
of the cerebral cortex
• If we use a particular part of our body more,
the area of cortex corresponding to the area
will increase in size (Elbert et al., 1995)
• If a region of the body is lost, the area of cortex
corresponding to the region will decrease in size.
– In people with upper extremity amputations, much of
the region of the cortex that use to correspond to the
U/E becomes reorganized. The area can then provide a
presentation of the face.
• This reorganization occurs through the unmasking
of silent synapses
• Similar brain reorganization is thought to
occur in people who are blind or deaf
– People who are congenitally deaf often have
enhanced peripheral vision to moving objects
– People who are blind use visual areas of cortex
when reading Braille writing
Complications of Reorganization
• May see referred sensations after an
amputation
– Stimuli that are applied to one area of the body
are felt to occur in a different part of the body
– A touch to the chin may be felt as if it were
applied to a missing fifth finger
• Functional reorganization may also be a
factor in some chronic pain syndromes,
where pain persists after the injury heals.
Factors that can influence
neuroplasticity
• Neuronal activity
– Overstimulation of somatosensory pathways
causes the increased release of inhibitory
neurotransmitters
– If there is understimulation of sensory
pathways, the cortex can become more
sensitive to weak stimuli
• Reduced activity can promote axonal growth to
increase stimulation
Factors that can influence
neuroplasticity – Growth Factors
• Brain-derived neurotrophic factor (BDNF)
– Supports survival of sensory neurons, basal
forebrain cholinergic neurons, and
mesencephalic dopaminergic neurons
– May be of use in local treatment of
neurodegenerative disorders (Parkinson’s
Disease)
– May be of use in protecting motor neurons in
patients with motor neuropathies and ALS
Growth Factors Continued
• Nerve Growth Factor – NGF
• May have a role in treating
– Alzheimer’s Disease – protects cholinergic
neurons in primates
– Diabetic neuropathy
– Chemotherapy-induced neuropathies
• May promote neuroplasticity
Overview of Neuroplasticity
• Defines how the nervous system responds
to:
– Injuries
– Changes in neuronal activity
How does neuroplasticity affect
the treatment of patients with
CNS injuries
• Forced-activity
• Excito-toxicity
Forced Activity
• Patient has an injury to the central nervous
system. The studies in humans have mostly
involved patients with strokes
• Patient is made to use the affected body part
• Studies have been done with people and
animals
Kozlowski et al., 1996
• Lesion to sensorimotor cortex
– Forced use of limb immediately after lesion
• Lesion increased in size: Excitotoxicity
• Long-term behavioral deficits
– Poor limb placement
– Decreased response to sensory stimulation
– Defective use of limb for postural support
Nudo et al., 1996
• Also in animals
– Small lesion in cortex associated with hand movements
• See loss of function from lesion site
• Also loss of function in adjacent, undamaged cerebral cortex
– Initiated movement 5 days after lesion
• Prevented loss of function in area adjacent to lesion
• In some animals, neural reorganization: hand representation
extended into regions which previously represented shoulder
and elbow
Human Studies
• Most done by one research group and its
students
• Stroke patients
– Restrain unaffected upper extremity
– Practice tasks with affected extremity
• Chronic stroke: > 1 year of dysfunction
• Results: See motor improvements
Why could constraint therapy
work?
• Learned helplessness
Excitotoxicity
• Too Much Of A Good Thing
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Ischemia or TBI
Release and Spread of Glutamate
NMDA receptors – Ca++ influx
Too much Ca++ can kill neurons
Extension of region of neuron death