Phys Neuroplasticity Flashcards
Axonal Injury (PNS):
4 Steps
(Discuss Wallerien Degeneration)
- Axon retracts away from post synaptic cell
- Wallerian Degeneration - myelin sheath gets peeled away and axon retracts further
- Glial cells/macrophages come in and eat up debris to prep area for axon to regrow
- Schwann cells guide axon to appropriate target
Axonal Sprouting:
Collateral -
Regenerative -
Collateral - new branches formed from neighboring cells
Regenerative - damaged axon regrows itself
(In adults, growth is slow and not precise)
Axonal Injury (Central CNS): 2 Causes
Causes:
1. Decreased Blood Flow (Ischemia)
2. Neurodegenerative Disease (MS, PD)
(CNS axons typically do not re-grow after injury)
Why doesn’t CNS regenerate?
CNS damage triggers…
- CNS damage triggers necrosis (cell death directly related to injury) and apoptotic cell death (secrete chemicals that kill healthy neighbor neurons) of severed axons.
Why doesn’t CNS regenerate?
Clean-up…
- Clean-up is slow:
- Lack of Schwann Cell Guidance
- Lack of Macrophages
Why doesn’t CNS regenerate?
CNS environment is hostile to regenerative attempts:
Astrocytes -
Microglial Activation -
Astrocytes - when healthy, secrete proteins for health and homeostasis
- Glial scarring -> come to area of injury and form a scar that stops physically and chemically downstream effect of chemical death (stop further infections, stimulate revascularization, will stop growth)
Microglial activation - when healthy, immune cell that helps with tissue homeostasis
- Problem -> can’t distinguish between debris and other supportive structures and difficult to control
Neurogenesis -
- Low level of GLIAL cells that can proliferate throughout our lifetime, except in two areas of brain:
1. Olfactory bulb (smelling)
2. Hippocampus (memory/learning)
What is neuroplasticity?
How can it be activated?
- Ability of nervous system to respond to intrinsic stimuli by reorganizing its structure, function, and connections
- Can occur during development, in response to environment, in support of learning, in response to disease, or in relation to therapy
Neuroplasticity Mechanisms:
Chemical
Chemical - brain increase NT it releases -> activate new postsynaptic receptors
- Can occur quickly
- Short term memory unless add additional support
Neuroplasticity Mechanisms:
Structural
Structural - Sustained changes can cause changes in axons
- Takes more time
- More long lasting (long term retention of new ability)
Neuroplasticity Mechanisms:
Functional
Functional - neurons can completely adopt new functions/roles when stimulated in specific way
(How we can survive neuro injury and how we see improvements)
Cortical Remapping:
Synaptic Pruning
(Examples)
-Example of functional neuroplasticity
Synaptic Pruning - eliminates/changes synapses based on what brain is being taught
Ex: Blindness - amount brain controls hand increases because necessary to read brail and increased senses to brain to compensate
EX: Phantom Limb - sensory aspects spill over into regions
Habituation -
What is it?
- Simplest form of neuroplasticity
- decrease response to repeated, benign stimulus (acclimation to light until you can tolerate)
- Allow’s us to pay attention to what’s important (tune out white noise)
Short term vs Long term Habituation
Short term = <30 min
-Presynaptic in nature -> dump less NT -> blunts AP
-After stimulus is over-> changes will go away
Long term = >30 min
-Changes in postsynaptic -> receptors and proteins that sustain AP
-Long lasting structural changes
Clinical Applications of Habituation:
EX: Peds - child doesn’t like hot/cold, so repeat stimulus and gradually increase and child will become less sensitive
EX: Vestibular dysfunction - dizzy/unsteady when turn head, so repeat exposure to head turn and slowly increase gradually and it will decrease sensitivity
Learning and Memory:
Experience-Dependent Plasticity -
- CNS uses experiences and modifies synaptic connections by increasing some while weakening others
- After injury -> brain will attempt to restructure
- More complex than habituation
Long-term potentiation (LTP) -
What is it?
What type of intensity required?
- Process by which the synaptic connections between neurons become stronger by frequent activation
- Requires high intensity stimulation
LTP: Low intensity exposure - Discuss mechanism (what receptors and what ions) Is there structural change?
- Few NT into synaptic cleft
- Glutamate binds to NMDA and AMPA receptors - > open post synaptic membrane
AMPA - Na+ flood into negative post synaptic cleft
NMDA - Some Na+/mostly Ca++, however Mg blockade - Receptors stay open as long as there is glutamate
- No structural changes
LTP:
High intensity exposure -
Discuss mechanism
Coincidence receptors -
- Increase glutamate release into synaptic cleft so receptors stay open longer
AMPA - increase Na+ into post synaptic cell
NMDA - electrostatic repulsion repels Mg+ blockade because of Na+ increase in post synaptic cell -> Ca++ enters cell
-Coincidence Receptors - both presynaptic increase of AP frequency and post synaptic electrostatic repulsion need to occur for it to become functional
Role of Calcium in high intensity exposure (3) 1. Secondary messenger 2. Increase strength 3. Increase growth
- Influx Ca++ acts as secondary messenger -> activates secondary cascade that initiates structural changes for long term effect
- Increase strength: activates increase AMPA receptors for future depolarization (more sensitive to glutamate and increases response)
- Increase growth: increase growth factors (proteins) that are involved in growth of new synapses
Long Term Depression -
What is it?
How does it stop long term potentiation and weaken activation?
- Conversion of active synapses into silent ones
- “Reset” button
- Low intensity, prolonged stimulation -> not enough to removed Mg blockade (so no LTP) and will remove AMPA receptors from post synaptic cell (weakens activation)
4 Ways you can use for Rehabilitation and Neuroplasticity:
- Technology
- Pharmacology
- Physical Rehab
- Cognitive Training
Ten Principles of Neuroplasticity: (1-5)
- Use it or lose it
- Use it and improve it
- Specificity matters (interventions specific to goal)
- Repetition matters
- Intensity matters
Ten Principles of Neuroplasticity: (6-10)
- Time matters (<6-12 months post injury ideal)
- Salience matters (should be important/meaningful)
- Age matters
- Transference or generalization (interventions cover many functions)
- Interference (start as soon as possible)
