Neuroplasticity (& its Manipulation in Research And Therapy) Flashcards
What is maladaptive plasticity?
Pathological plasticity in the NS, leading to disruptions of function.
Name some examples of physiological AND psychological disorders caused (or influenced) by maladaptive plasticity?
Physiological:
- Phantom limb pain
- Tinnitus
- Chronic pain
- Musician’s dystonia
Psychological:
- Addiction
- OCD
- Chronic stress
Musician’s dystonia is a type of focal, occupational dystonia. What do these terms imply about the condition?
- Dystonia: Painless loss of muscular control
- Focal: Localized to a specific body part
- Occupational dystonia: Task-specific focal dystonia
- Musician’s dystonia: Resulting specifically from musical training
How does musician’s dystonia occur as a result of maladaptive plasticity?
Due to overtraining, neuronal connections corresponding to trained body parts (e.g. hands in pianists) in the Somatosensory and the Motor Cortex grow beyond their boundaries, leading to overlapping cortical representations for individual muscles, and thus, loss of control of discrete control.
Neuroplasticity
- involves strengthening, reorganisation, pruning and neurogenesis
- learning and memory
- response to injury
- rehabilitation potential
- adaptation to change
- neurogenesis
–> dynamic brain
London Taxi divers
Hippocampal study
- MRI scans to compare between London taxi drivers with non-taxi drivers
- taxi drivers had larger posterior hippocampi (linked to spatial memory) and smaller anterior hippocampi
Implication
- experience-dependent plasticity -> brain physically changes with long-term experiences
- functional specialisation -> different hippocampus regions have distinct roles
- real-world application -> supports targeted learning, therapy, skill development
Types of neuroplasticity
1) Structural plasticity
= physical changes in the brain’s structure
Mechanisms
- neurogenesis
- synaptic remodelling
- dendritic branching
2) Functional plasticity
= reorganisation of brain functions in response to experience
Mechanisms
- neural pathway reorganisation
3) Short term plasticity
= immediate, temporary changes in synaptic strength
Mechanisms
- synaptic facilitation
- synaptic depression
4) Long term plasticity
= enduring changes in synaptic strength and structure
Mechanisms
- Long term potentiation
- long term depression
Hebbian vs homeostatic plasticity
1) Hebbian plasticity
= change of the synaptic strength (+/-) depending on the level of neuronal activity after stimulation
- rapid changes (seconds to minutes)
- activity-dependent strengthening
- positive feedback mechanism
- can lead to network instability if unchecked
2) Homeostatic plasticity
= synaptic changes that counter balance those induced by hebbian plasticity
- slower changes (hours to days)
- compensatory mechanisms –> ion channel density, transmitter release or postsynaptic receptor sensitivity
- negative feedback system
- synaptic scaling
- maintains network stability
Network architecture to molecular control
Network level
- modular organisation
- circuit stability
- functional redundancy
Bridge mechanisms
- activity-dependent changes
- homeostatic control
- gene expression control
Molecular level
- CREB signalling
- gene transcription
- protein synthesis
Long-term potentiation (classical path, LTP)
- release of serotonin
- synthesis of cAMP (cyclic AMP a messenger) - activation of PKA (Protein Kinase A)
- if pathway is repeatedly stimulated, the amplitude of EPSP is constant - CREB phosphorylation at Ser133
- Gene transcription
- structural changes (greater number of branches)
Sea slugs to humans
- similar modular cascades across species
- shared role of second messengers
- common structural changes
- comparable gene regulation patterns
lasts up to 1 year
Different pathways to CREB activation
- The classical path: cAMP/PKA pathway
- discovered in Aplysia study - The activity-dependent path: Ca2+/CaMK pathway
- tiggered by neural firing - The development path: growth factor pathway
- important for neural growth and survival
not all phosphorylation is equal
1. cAMP-induced phosphorylation is most efficient
2. growth factor pathways less efficient
Long-term depression (LTD)
= characterised by activity-driven, enduring reductions in synaptic efficacy
Functions
- increasing synaptic ranges in which synapses can operate
- preventing synapses from entering states of saturation
- encoding distinct aspects of memory-inducing events
- adjustment of synaptic weights to refine memory
lasts up to hours or days
Postsynaptic currents
- action potential
- voltage-dependent Ca2+ channels open
- increase in intracellular Ca2+ in the presynaptic terminal
- release of neurotransmitters
- process triggers an electrical response in the postsynaptic neuron
Excitatory effects
- increases the probability of postsynaptic spiking
- generating excitatory postsynaptic potential (EPSPs) through positive membrane potential deflection
Inhibitory effects
- decreases the probability of postsynaptic spiking
- producing inhibitory postsynaptic potentials (IPSPs) through negative membrane potential deflection
Short term facilitation (STF)
= synaptic efficacy increases for brief periods
Temporal dynamics vary
1. paired-pulse facilitation (milliseconds)
2. synaptic enhancement (hundreds of milliseconds)
3. augemntation (seconds)
4. post-tetanic potentiation (minutes to hours)
Mechanisms
- Ca2+ accumulation in the presynaptic terminal after AP –> increases the amount of released neurotransmitter in the subsequent AP occurs close enough in time
Short term depression (STD)
= a temporary decrease in synaptic strength that occurs when neurons are repeatedly activated
Linked to
- habituation
- sensory adaptation
Mechanisms
- depletion of synaptic vesicles –> high frequency of AP depletes the vesicles available over time
- decreased Ca2+ –> inactivation of Ca2+ channels
- endocannabinoids –> retrograde signal that closes calcium channels
