SLE2/MODULE 5- Neuroplasticity Flashcards
the nervous system is constantly ____
changing
-possibly due to positive things (learning new tasks)
-or not so positive things (disease, aging, injury)
recovery depends on the ability of neurons to do what
to reinnervate appropriate targets
2 ways that neurons reinnervate appropriate targets
-axon regeneration
-collateral sprouting
axon regeneration
regeneration of injured axons
collateral sprouting
surviving axons developing sprouts to reinnervate abandoned targets
axotomy
axon cut
see slide 6
axotomy results in
degenerative changes within the axon DISTAL to the legion (distal to where the cut is) + the associated neuron
axotomy- a few days after the cut/lesion occurs, what do we see
progression of the black substances (ex: axon + myelin fragments) move about
-Nissl substances break apart + moves to the periphery of the soma; this movement is what will promote the regeneration + ability of sprouting down the axon that is so important to recovery
what does recovery depend on
the ability of the axonal sprouts to reinnervate appropriate targets
-so the nature of the injury is vital to success
motor unit
refers to the motor neuron projecting from the spinal cord, its axon, + all the muscle fibers that the neuron innervates
3 types of neuron injury
-complete transection
-partial denervation
-crush injury
collateral sprouting
axons of surviving motor units develop sprouts to reinnervate the muscle fibers that have been denervated
collateral sprouting is confined to what area
distal region of motor axon
-occurs close to the target
with collateral sprouting, motor units can enlarge up to ____x the original size
5x
see slide 8 graphs
what can explain greater force?
a) increased number of fibers innervated
b) large muscle fiber areas
c) greater maximal muscle force per cross-sectional area
d) a + b
e) all of the above
e) all of the above
-if I have more fibers innervated, I have a bigger muscle, which means larger muscle fiber area, which means greater amount of force for a given cross-sectional area
neuropathies
disorder of PERIPHERAL NERVES
**neuropathies are peripheral or central nerves
peripheral
where does the motor axon originate/come out from
spinal cord
neuropathies are acute/chronic
can be either
neuropathies involve myelin sheath/axon
either
what is one of the most common neuropathies
diabetic neuropathy
-has to do with blood vessel inability to provide nutrient to the nerve of interest
Guillain-Barre syndrome
autoimmune disorder that disrupts myelination of peripheral nerves
-causes neuropathy
what type of neuropathy is caused by Guillain-Barre syndrome
rapid-onset acute neuropathy
primary symptoms of Guillain-Barre syndrome
-muscle weakness
-tingling (paralysis)
exact cause of Guillain-Barre syndrome
unknown
-campylobacter infections (doctors think this disease may be caused by a bacterial infection you can get through food poisoning)
who has Guillain-Barre syndrome
Travis Frederick of the Dallas Cowboys
2 autoimmune diseases
-GBS (Guillain-Barre syndrome)
-MS (multiple sclerosis)
GBS damages PNS/CNS
PNS
MS damages PNS/CNS
CNS
autoimmune
body’s immune system attacks its own tissues
how does GBS often start
post-infection (i.e. respiratory or digestive tract)
how does MS often start
likely due to:
-infections (i.e. Epstein-Barr virus or herpes)
-genes
-vitamin D deficiency
-smoking
GBS common symptoms
-weakness
-numbness
-tingling in limbs
MS common symptoms
-weakness
-numbness
-tingling in limbs
GBS prognosis
-severe symptoms
-full recovery possible
MS prognosis
lifelong disease
-varying symptom duration
can someone have GBS + MS at same time
very rare but not impossible
-coincidence if it does occur
similarities between GBS + MS
both are:
-de-myelinating conditions
-influence the nervous system
-autoimmune
neurogenesis
ability to generate neurons
neurogenesis may have what concerns
ethical
neuroplasticity in response to disease
-possibility to transform skin cells into induced pluripotent stem cells + then differentiate into neurons
-cultured human neurons with potential therapeutic application to neurological disorders + injuries (Alzeimer’s, Parkinson’s, Huntington’s, Epilpsy, Stroke)
-neurogenesis may have ethical concerns + therefore isn’t a common response to some of these diseases
neuroplasticity in response to injury
-largely involves synaptogenesis
neuroplasticity occurs at what 2 levels
-individual
-population
**population level of neuroplasticity
changes in:
-thickness
-volume
-density
functional changes of neuroplasticity have to do with
activities that pertain to electrical signals being transmitted or some sort of neurotransmitter crossing a synaptic cleft
neuroplasticity functional changes (3)
-EPSP/IPSP
-synaptic activity
-intrinsic excitability
EPSP/IPSP
the electrical response to a depolarizing/hyperpolarizing singal
synaptic activity
the release of vesicles neurotransmitters
intrinsic excitability
excitability inherent to the neuron
structural changes of neuroplasticity have to do with
the actual properties you can look at under a microscope
neuroplasticity- structural changes (4)
-dendritic arbors
-spine density
-synapse number + size
-receptor density
dendritic arbors
growth of little dendrites + sprouts
spine density
size of spines + sprouts
synapse number + size
you can evaluate + measure with tiny rulers in your microscope
receptor density
number of receptors you have
(if I take a certain drug will I have more synapses/more receptors? if i have this injury occur, will there be changes to the structure of my system?)
where do changes from neuroplasticity take place (2)
-synapse (synaptic)
-cell (structural)
neuroplasticity changes at synapse
-changed amount of neurotransmitter released for each AP discharged at axon terminal
-at postsynaptic membrane, changed number of receptors for neurotransmitter, type of neurotransmitter receptors, or second messenger release
neuroplasticity changes at cell (structural) level
change in number of synapses (dendrites, branches, length) or even numbers of neurons (sprouting, pruning)
neuroplasticity changes at synapse are short/long term
can be either
neuroplasticity changes at cell (structural) are short/long term
long term
which of these is the best example of structural neuroplasticity at the population level?
a) increased acetylcholine release at a neuromuscular junction
b) calcium release due to a G-protein couple receptor effect within a neuron
c) greater presynaptic inhibition by one neuron projecting onto another
d) increased grey matter volume
e) one neuron’s synapses become larger
d) increased grey matter volume
estimating structural adaptations
it is possible to measure thickness of selected brain regions as an index of ____
dendritic content change
estimating structural adaptations
how are functional changes measured
-extracellular recordings of field potentials (EEG, evoked potentials)
-imaging (fMRI, PET)
estimating structural adaptations
measuring what of the cerebral cortex reveals changes
size of sensory + motor maps of cerebral cortex
motor map
looks at changes in cortex related to motor functions
(if you acquire a motor skill like cup stacking, you should be able to see changes in the motor map associated with the action but in your brain)
sensory map
generating by looking at brain activity/responses to incoming stimuli
(whereas motor maps are made by directly stimulating the brain itself)
motor maps in the cortex can be measured with ____
intracortical microstimulation
3 ways motor maps in the cortex are measured with intracortical microstimulation
-areas of the cortex in which stimulation evokes movement
-placement of the stimulating electrode
-trans-synaptic activation of corticospinal neurons
3 ways cortex motor maps are measured w/ intracortical microstimulation
areas of cortex in which stimulation evokes movement
motor map of the cortex, shows areas of the cortex where stimulation happened that evoked movement
-we see the movements are associated with the whisker of a rodent in pink, we see there is a change that occurred distally in green, etc.
3 ways cortex motor maps are measured w/ intracortical microstimulation
placement of the stimulating electrode
we see placement of the stimulating electrode via the needle like thing in the transection related to the nervous system
3 ways cortex motor maps are measured w/ intracortical microstimulation
trans-synaptic activation of corticospinal neurons
we see trans-synaptic (trans = across) activation of corticospinal neurons; looking at motor maps + changes you can see in
-response to the stimulus at the CNS in the spinal cord + how that affects a bunch of different neurons
several weeks of skilled reach training increased what 2 things in rat motor cortex
-size of distal motor map
-increased synaptic density
much more increase for skilled or unskilled reaching for rodent motor cortex
SKILLED
explain how rat housing conditions influenced neuron structure
much more extensive branching in enriched castle
-raised cortical neurons
-more extensive dendrites + dendritic spines
motor recovery depends on changes in ____
synaptic function
what 2 ways is motor recovery/rehabilitation accomplished
-recovery
-compensation
recovery
-restoration of function in neural tissue that was initially lost due to injury/disease
-usually explained by gradual removal of responses to injury (edema inflammation, blood flow disturbance)
ex: I experience an injury at the gym + with time I am able to recover fully/close to fully
what is the most common way that acute injuries are responded to
recovery
compensation
-residual neural tissue takes over a function that has been lost due to injury/disease
-possibly due to redundancy that exists in the cortex
ex: I can get a sensory/motor map in multiple areas of certain regions of the brain + can see that there are regions of the brain dedicated to the same task/sensory response
-SO if one area is damaged, I can use another area to compensate for the damaged area to make sure I don’t lose the ability to do an action
compensation is due to ____
redundancy
example of RECOVERY after loss of function in residual neural tissue after an injury
-after the stroke, the rodent is not able to move the forelimb/activate the associated regions of the brain to do the forelimb movement as well as it did before the stroke
-not all is lost because there are SOME regenerations/recovery only 24 hours after + with time there will be more
*motor map via intracortical microstimulation (ICMS) of forelimb movements (green) in rat motor cortex before (left) and 24 hrs after (right) focal stroke (dotted line)
*loss of movements outside stroke area was accompanied by a loss of synapses (graph) at 24 hrs after the stroke
example of COMPENSATION after injury
-a stroke as induced, + rather than recovering the same areas as before, the brain compensated for the now damaged locations
*motor maps for hand movements in the ventral premotor cortex (PMV) of a monkey before and after a stroke
*hand representation in the PMV increased in size after the stroke
*the PMV became more involved in hand movements than it was before the stroke
when is functional improvement the greatest
when it involves recovery
-nothing is as great as fixing what has already been damaged (ex: teacher is out sick, no one can replace the teacher the same way as if the teacher came back)
when is functional improvement the least
when it is based on compensation
strategies to improve motor function (3)
-restoration
-recruitment
-retraining
strategies to improve motor function- restoration
refers to activating brain areas in which function has been compromised
-progressive but doesn’t begin until after injury
**strategies to improve motor function- restoration involves recovery/compensation
recovery
strategies to improve motor function- recruitment
-enlists brain areas with the ability to produce motor function but are not involved in action pre-injury
-occurs when damage to neural tissue cannot be resolved
-is not due to secondary effects of injury
**strategies to improve motor function- recruitment involves recovery/compensation
compensation
-but does not involve learning new functions
strategies to improve motor function- retraining
form of compensation in which residual neural tissue is required to learn a new function
**strategies to improve motor function- retraining involves recovery/compensation
compensation
pre-stroke + post-stroke groups with no motor rehabilitation vs motor rehabilitation
several days of training on the forelimb reaching task restored both movement representations and synaptic density
pre-stroke + post-stroke groups with no motor rehab vs motor rehab
compare both pre-stroke panels
not a big difference between motor rehab vs no motor rehab
pre-stroke + post-stroke groups with no motor rehab vs motor rehab
compare post-stroke panels
motor rehab is much more successful than no motor rehab
which statement about neural plasticity is incorrect?
a) enriched housing increases the size of motor maps
b) it is unlikely that the region of an evoked stroke will be recovered with rehabilitation
c) sensory maps are measured by stimulating peripheral receptors + measuring the cortical response
d) unskilled reaching increases the motor maps for distal muscles
e) specific movement training like reaching tasks by rodents can influence motor maps
d) unskilled reaching increases the motor maps for distal muscles
LTP
long term potentiation
LTP increases what
size/amplitude of EPSPs
-and generates new dendritic spines
LTD
long term depression
what is the key factor underlying changes in motor + sensory maps
changes in synaptic function
what is the most characterized change in synaptic function
LTP + LTD
what 3 things does LTP depend on
-intensity
-repetition
-timing of the activating signal
intensity
how QUICKLY we stimulate
-aka rate of stimulation
change in EPSP amplitude in rat hippocampus slice depends on what
rate of stimulation (aka intensity)
tetanic stimulation at a lower/higher frequency augments EPSP more
higher frequency
-lower frequency does go up but not very much
-so in response to that the system drops + the EPSP becomes smaller
-after the stimulation stops that deduction below the baseline value is LTD
higher LTP…
the longer it will stay
LTP in the rat cortex was greater after receiving the stimulation for 1 day or 5 days
5 days
-this indicates the influence of REPETITION
coactivation
2 neurals input at same time, concurrent input
-output is strengthened
what 4 things does synaptic strength depend on
-quantity of neurotransmitter
-number of postsynaptic receptors
-synapse size
-number of synapses
salience
the quality of being particularly noticeable/important
-aka the prominence/significance of the test we are doing + the intervention induced to it
occipital
related to vision
frontal cortex
related to being able to name different objects
besides intensity, repetition, + timing what 2 things does neural plasticity depend on
specificity + salience of the intervention
rats trained on 4 tasks produced specific adaptations- visuospatial learning (Morris water maze)
increased dendritic length + branching on pyramidal cells in occipital cortex
rats trained on 4 tasks produced specific adaptations- object recognition
increased dendritic branching + spine density in frontal cortex
rats trained on 4 tasks produced specific adaptations- skilled reaching
increased dendritic legnth + branching in contralateral forelimb cortex
rats trained on 4 tasks produced specific adaptations- bilateral string pull
same changes in both sides of cortex
experiment- rats trained to discriminate between frequency + loudness
test of salience
-all of the rodents received recordings related to frequency + loudness; but the rodents were specifically trained on only ONE of them
-control group- had no training on either frequency or loudness discrimination
-frequency discrimination group- only trained on frequency / vice versa for loudness discrimination group
-map is way bigger in frequency discrimination group than the loudness discrimination group for the frequency map
which factor does not influence the size of LTP?
a) intensity
b) timing
c) repetition
d) number of dendritic spines
e) salience
d) number of dendritic spines
because number of dendritic spines is typically part of the output
neural plasticity provides a foundation for ____
neurorehabilitation
training can increase the size of what 3 things
-motor maps
-sensory maps
-visual maps
how do map changes reflect adaptations
in the number, density, + function of synapses
what 4 things does synaptic plasticity (e.g. LTP) depend on
-intensity
-repetition
-timing
-salience
(of the activating signal)
functional improvements are possible, with a preference for recovery/compensation
recovery
