11. Neuroplasticity, Learning, and Injury

What are the three broad phases of neuroplasticity after injury?

First 48 hours, week 1-2, and weeks to months

What happens to brain tissue in the first 48 hours after injury?

Initial damage accumulates as cell death occurs and cortical pathways are lost

What types of cellular damage can occur immediately after brain injury?

Apoptosis, necrosis, phagocytosis, membrane breakdown, inflammatory cytokines, edema, and excitotoxicity

What may the brain try to do immediately after injury to preserve function?

Use secondary neuronal networks

What happens during week 1-2 after brain injury?

The brain begins structural repair through glial support, debris clearing, inflammation regulation, and pathway rebuilding

What role do glial cells play during week 1-2 after injury?

They clear debris, regulate inflammation, and support rebuilding of pathways

What begins during week 1-2 after injury?

Synaptic plasticity begins as circuits shift activity patterns

How can synaptic plasticity be harmful early after injury?

It can be harmful if inhibitory systems become overly excitatory

Why does early rehabilitation matter after brain injury?

Repeated meaningful activity helps guide which connections strengthen

What happens weeks to months after brain injury?

Long-term brain reorganization and function restoration can occur

What mechanisms support long-term brain reorganization weeks to months after injury?

Axonal sprouting, collateral sprouting, synaptic reorganization, LTP, LTD, and functional reorganization

What is axonal sprouting?

Growth of new axon branches after injury or repeated activity

What is collateral sprouting?

Nearby intact axons send branches to denervated targets

What synaptic mechanisms help reorganize circuits after injury?

Long-term potentiation and long-term depression

What is functional reorganization after brain injury?

Other brain areas help take over lost functions

What is equipotentiality or vicariation?

The ability of other brain areas to help take over lost functions

What is habituation?

A decreased response to a repeated, non-threatening stimulus

What happens in the nervous system during habituation?

The nervous system filters out stimuli that are not important

Why is habituation useful?

It conserves nervous system resources

What is an example of habituation?

Tuning out background sounds after hearing them for a while

What is sensitization?

An increased response to a stimulus after repeated or intense input

What changes can occur during sensitization?

Increased presynaptic release, increased postsynaptic response, and stronger excitatory signaling

How can sensitization affect pain?

It can amplify noxious input or make normally non-painful input feel painful

What is LTP?

Long-term potentiation

What does LTP do to synaptic transmission?

It strengthens synaptic transmission over time

What is LTP important for?

Learning and memory formation

What neurotransmitter is involved in LTP?

Glutamate

What receptors are involved in LTP?

AMPA and NMDA receptors

What does glutamate do to AMPA receptors during LTP?

It activates AMPA receptors and depolarizes the postsynaptic membrane

What does depolarization do to NMDA receptors during LTP?

It removes the Mg2+ block

What happens after the Mg2+ block is removed from NMDA receptors?

Ca2+ enters the postsynaptic neuron

Why is Ca2+ influx important in LTP?

It triggers intracellular signaling that strengthens the synapse

How does LTP strengthen a synapse?

Through AMPA receptor changes, gene expression, structural changes, and more efficient future signaling

What is LTD?

Long-term depression

What does LTD do to synaptic strength?

It persistently decreases synaptic strength

How can LTD weaken a synapse?

By decreasing neurotransmitter release or reducing the number or efficiency of postsynaptic receptors

Why is LTD important for neuroplasticity?

It prunes and refines circuits by weakening redundant or unnecessary connections

How does LTD help learning?

It weakens less useful connections so more useful connections can be strengthened

How can axonal sprouting help recovery?

It can find new pathways and reconnect circuits

How can axonal sprouting hinder recovery?

It can create inaccurate connections that cause maladaptive plasticity, pain, sensory confusion, or synkinesis

What is maladaptive plasticity?

Neuroplastic change that worsens function or creates abnormal symptoms

What is synkinesis?

Unwanted movement that occurs with intended movement because of abnormal or miswired connections

How does collateral sprouting relate to neuroplasticity?

It restores partial function by recruiting alternative pathways

Why is collateral sprouting experience-dependent?

Meaningful, challenging practice helps shape useful connections

What is Wallerian degeneration?

Degeneration of the distal axon segment after an axon is severed

What happens to the distal axon segment after an axon is severed?

It degenerates because it is disconnected from the cell body

What must happen before regeneration can occur after Wallerian degeneration?

Debris must be cleared

What cells help clear debris and guide regrowth in the PNS?

Schwann cells

How do Schwann cells support peripheral nerve regeneration?

They help clear debris and guide regrowth through preserved connective tissue tubes

What can happen if supporting structures are disrupted during axon regeneration?

Recovery is slower and neuroma or miswiring can occur

What can happen if an axon regenerates incorrectly?

Neuroma, miswiring, or slower recovery can occur

What do AMPA receptors do?

Provide fast excitatory glutamate transmission and help depolarize the postsynaptic neuron

What do NMDA receptors do?

Allow Ca2+ influx after depolarization removes the Mg2+ block

Why are NMDA receptors voltage-dependent?

They are blocked by Mg2+ at resting membrane potential and open after depolarization removes the block

What ion enters through NMDA receptors after the Mg2+ block is removed?

Ca2+

How does Ca2+ signaling affect synapses?

It helps determine whether synapses strengthen through LTP or weaken through LTD

What determines whether Ca2+ signaling leads to LTP or LTD?

Activity patterns

What is a silent synapse?

An immature excitatory synapse with NMDA receptors but few or no functional AMPA receptors

Why is a silent synapse inactive at resting membrane potential?

NMDA receptors are blocked by Mg2+ and there are few or no AMPA receptors to signal effectively

How is a silent synapse activated?

Depolarization removes the Mg2+ block from NMDA receptors, Ca2+ enters, and AMPA receptors are recruited or inserted

What does it mean to “unsilence” a synapse?

AMPA receptors are added so the synapse can contribute to signaling

What can activated silent synapses contribute to?

New learning, skills, memories, or recovery

What is excitotoxicity?

Neuronal damage or death caused by excessive glutamate release or overactivation of AMPA and NMDA receptors

How does glutamate overactivation cause excitotoxicity?

It causes excessive Ca2+ influx and disrupts ion balance

What does excessive intracellular Ca2+ trigger during excitotoxicity?

Damaging enzymes, mitochondrial injury, free radicals, inflammation, membrane breakdown, and neuronal death

Which receptors are overactivated in excitotoxicity?

AMPA and NMDA receptors

What is the final result of severe excitotoxicity?

Neuronal death

What is the easiest way to remember habituation?

Repeated safe stimulus leads to a smaller response

What is the easiest way to remember sensitization?

Repeated or intense stimulus leads to a bigger response

What is the easiest way to remember LTP?

Long-term potentiation strengthens useful synapses

What is the easiest way to remember LTD?

Long-term depression weakens unnecessary synapses

What is the easiest way to remember Wallerian degeneration?

The distal axon segment dies after being cut off from the cell body