19.4 + 24.6. Repair and Plasticity (HT) Flashcards
1
Q
What is meant by plasticity?
A
- Generally speaking, it is a quality of being easily shaped or moulded
- In biology, it refers to the ability of an organism to adapt to changes in the environment
- In neuroscience, it refers to the ability of the nervous system to show lasting changes in its structure and/or function in response to internal or external constraints
2
Q
What are the 7 levels of organisation within the nervous system?
A
- Different levels are interlinked/have effects on each other
- It is often best to chose a marker that reflects the question best, as change is likely to occur on all/most levels
3
Q
What are the two types of plasticity, and when are they relevant?
A
- Experience-expectant plasticity is relevant in the developing CNS (selective stabilisation, dependent on expecting experiences and results in the formation of many synapses, but only a few are retained/most are pruned)
- These are related to universal experiences undergone by all people, such as plasticity in response to movement or visual input
- Experience-dependent plasticity is seen in localised regions of the CNS, and is involved in the processing of specific experiences
- E.g. repeated experiences will cause changes within the CNS
4
Q
Give an example of enlargement of brain region on the basis of performance.
[EXTRA]
A
- London Cab Drivers case
- Hippocampus is a region of the brain specific to memory and spatial navigation
- Structural MRIs of the brains of liscensed London Taxi drivers were analysed and compared with those of matched controls who did not drive taxis
- Changes measured in both anterior and posterior hippocampus
- Found that both left and right posterior hippocampi were found to be enlarged compared to controls
- Changes in increased hippocampus size also positively correlated with the time spent as a taxi driver
- This indicates possible local plasticity within a healthy adult brain as a function of increased exposure to an environmental stimulus
- Also suggests that posterior hippocampus stores a representation of the environment which can increase as navigational skills are also increased
5
Q
What is the effect of musical expertise on the structural neuroplasticity of a musician’s brain?
[EXTRA]
A
- Functional and structural changes have been found using structural MRIs when comparing the brains of professional, semi-professional and non-musician subjects
- Primary motor cortex, planum temporale and anterior corpus callosum
- Most studies make it hard to assess whether the changes seen in brain structure are a product of nature (biological predisposition) or nurture/early training during critical periods of development
6
Q
Are structural differences in a professional musician’s brain likely to be nature, nurture or both?
[EXTRA]
A
- Study by Hyde et al 2009 investigated changes in brain development over 15 month period of experimental music training, found to drive structural brain plasticity in early childhood
- Significant expansion in the primary motor region was seen (right precentral gyrus)
- There was a positive correlation between the relative voxel size of the right precentral gyrus with a change in behavioural performance on a left-hand motor task after musical training
- This suggests that structural brain differences seen in professionals are likely to be due to training-induced plasticity, as was seen in taxi drivers
7
Q
Give an example of unwanted plasticity.
[EXTRA]
A
- Extensive musical training can result in fusion of somatosensory representations of single digits - focal dystonia
- Dystonia is a neurological condition affecting a muscle/group of muscles in the same region, causing involuntary muscular contractions and abnormal positioning (e.g. in hand, causes fingers to curl into palm or extend without control)
- This condition is associated with the repetitive, synchronised movements of digits made by musicians over many years of music
- Coronal MRI sections taken through somatosensory cortices of musicians with focal hand dystonia compared to control
- In dystonic patients, the contralateral side to the dystonia showed blurring between the regions stimulated by each of the fingers
- This indicates fusion of networks that process incoming sensory stimuli
- Regions for affected digits were also located far more closely together than they were on the unaffected side
- In dystonic patients, the contralateral side to the dystonia showed blurring between the regions stimulated by each of the fingers
8
Q
What is homologous area adaptation?
A
- Form of neuroplasticity that occurs during early critical stages of development
- If there is damage/a lesion during this stage, it can be compensated for by shifting the corresponding cell populations of the homologous region in the opposite hemisphere
- This can be seen in lesions of the motor cortex in young patients
- (Rados et al, 2013), lesion in left parietal lobe (particularly paramedian part of left central gyrus)
- Functional imaging indicates that motor cortex is only activated when feet carry out flexion on either side
- Reconstruction of the corticospinal tract also indicates thinning on the left side, and fibres from the left precentral gyrus are virtually absent
- These results indicate redistribution of function from the corresponding motor area of the contralateral hemisphere
9
Q
What is the trade-off between plasticity and stability in biological systems?
[EXTRA]
A
- Other experiments indicate that when input from one sensory modality is removed, other regions of the brain can compensate by increasing performance
- However, there is evidence to indicate that the switch is not complete, and some of the original connections remain
- Hand area of primary somatosensory cortex contains detailed finger topography thought to be shaped and maintained by daily life experience
- HOWEVER this is disproved in amputees, where some preserved representation of the missing hand is still seen (using ultra-high field neuroimaging), even after long periods post-amputation
- There is also the experience of phantom sensation
- If above postulation was correct, representation of hand in the brain would be lost or become indetectable over time
- Contrary evidence in amputees suggests that there is a degree of stability within the CNS, alongside the plastic capabilities
10
Q
What is the Hebbian theory of learning?
A
- ‘When an axon of cell A is near enough to excite cell B and repeatedly/persistently takes part in firing it, some growth process or metabolic changes takes place in one of both cells such that A’s efficiency, as one of the cells firing B, is increased
- Hebb, D. O., The Organisation of Behaviour, 1949
11
Q
What are the two key glutaminergic receptors?
A
- AMPA
- Works at all potentials and allows the inflow of Na+ once glutamate is bound
- NMDA
- Blocked by Mg2+ at RMP, meaning that (even if glutamate is bound), no current will flow through this channel until the endogenous blockade is removed
- Mg2+ is removed when the post-synaptic membrane is depolarised
- Both are ionotropic
12
Q
What is long-term potentiation (LTP)?
A
- A type of synaptic plasticity where the synapse becomes sensitised - in the hippocampus, for example, it causes an increased efficacy of the CA3 - CA1 synapse
- If tetanus occurs, there is an influx of Ca2+ as the NMDA receptors are unblocked
- This causes a maintained increase in the sensitivity of the synapse, due to an increase in the EPSP amplitude
13
Q
What is long-term depression (LTD)?
A
- This correlates to a decreased efficacy of the synapse (e.g. between CA3 and CA1 in the hippocampus)
- Occurs after low-frequency stimulation and is thought to deactivate certain synapses (thought to be a cellular level plasticity mechanism for forgetting)
- Continued low-frequency stimulation (1Hz for 15mins) results in depression of the EPSP for extended amounts of time
14
Q
What are some experimental methods of blocking LTP?
[EXTRA]
A
- Pharmacological blockade - e.g. use APV to selectively block NMDA receptors
- Transgenic manipulation - e.g. CRISPR-based genetic deletion of CaMKII protein
15
Q
What is a measure of synaptic strength and how can it be measured?
A
- Density of AMPA receptors on the post-synaptic membrane
- These receptors can function at all potentials, therefore if their number increases then the efficacy of synaptic transmission with also increase
- You can visualise this through tagging AMPA receptors on dendritic spines with GFP
- Can compare the frequency before and after tetanus/LTP
- It can also be observed that the dendritic spines grow after tetanus/LTP
16
Q
What are some structural changes that occur after LTP?
A
- LTP induces structural remodelling of synapses and formation of new contacts
- Functional changes often lead to structural changes, such as sprouting and pruning
- This can be measured by recording the size, shape and number of post-synaptic densities (PSDs) after LTP
- From small, simple PSDs, post-synaptic compartments grow in size and ultimately split into many spine boutons
17
Q
What are some examples of neuronal plasticity at non-synaptic sites?
[EXTRA}
A
- Intrinsic plasticity can be seen, involving enduring changes to the number, distribution or activation of ion channels central to the intrinsic excitability of neurons
- This shapes the flow of information within a neuron through impacting the threshold for synaptic changes and following the course of the synaptic inputs (from the dendrite to the axon terminal)
19
Q
What is an experiment for learning-related intrinsic plasticity?
[EXTRA]
A
- Formation of memory of nociception in association with a sound
- Nociception induced by an air puff onto the cornea which induces a blink response
- Electrode measurements of a specific neuron within CA1 were taken pre-learning, 24 hours after and 14 days after
- In the recordings, there is a drastic reduction of the after-hyperpolarisation potential of a CA1 neuron soon after learning
- This is not seen in naïve subjects or in subjects well after the initial learning
- The reduction of the after-hyperpolarisation potential allows for neurons to fire more spikes in a burst, therefore avoiding the typical spike-adaptation pattern that is normally seen
- This type of learning-induced intrinsic plasticity is transient, but could be a gateway mechanism for memory
22
Q
How are retinotopic maps on the superior colliculus (SC) organised?
A
- This occurs in several different stages and is guided by complex interactions between multiple processes
- Axon extension and overshoot
- Selective arborisation of RGC axons by the graded expression of various molecular cues in both the retina and the SC
- There is also axonal competition for collicular associations
- Activity-dependent plasticity of axonal arbours for map refinement
- This last process is linked to the spontaneous correlated activity of RGCs in the form of axonal waves
23
Q
How can RGC axons in the superior colliculus be visualised during development?
[EXTRA]
A
- Can inject axons focally with lipophilic fluorescent tracers (e.g. Dil) into temporal retina of a WT mouse to label all of the RGC axons from a single retinal location
- Use diagram:
- At P1, RGCs have entered the superior colliculus and have arborised across the whole axis
- NB the projections initially extend far more posterior than the location of their future termination zone (shown within the black circle)
- New branches will then form along the axonal shaft, as can be seen in P4
- RGC axons with terminal branches near the final termination zone have formed arbours
- At this point, many RGC axons have also eliminated their initial axonal overshoot
- At P8 there is a dense focal terminal zone for RBC axons, with elimination of the initial axonal overshoot, and arbours persisting outside of the termination zone
- At P8, the retinotopic map begins to resemble its final form
- Even at this point we can see that the topographic retinotopic map on the superior colliculus has required extensive remodelling
- At P1, RGCs have entered the superior colliculus and have arborised across the whole axis
30
Q
Describe how we can classify nerve fibre injuries.
[EXTRA]
A
- (Seddon, 1942) introduced the first classification of nerve fiber injuries, considering two clinical signs of damage (“Loss of Function” versus “Perversions of Function”) and continuity of fibers.
- This was then further refined by Sunderland’s classification, which provides 5 levels of damage, from slight, easily repaired damage to full nerve severance.
39
Q
Describe how cell therapies could be used to treat Parkinson’s disease.
[IMPORTANT]
A
- Stem cells can be sourced or induced
- These can be used to create new dopaminergic neurons
- These can then be transplanted into the patient, helping to alleviate symptoms
- However, there are difficulties with these approaches, especially because they do not stop the progressive loss of dopaminergic neurons
40
Q
What is Wallerian degeneration?
A
Wallerian degeneration is an active process of degeneration that results when a nerve fiber is cut or crushed and the part of the axon distal to the injury (i.e. farther from the neuron’s cell body) degenerates.
