Week 2 - Development, Aging, and Protein Accumulation [Possible Exam Questions]

Briefly describe neurulation and one way in which an error in neurulation can alter the developing brain

Neurulation is the early developmental process in which the neural plate folds around the neural groove to form the neural tube, which later develops into the brain and spinal cord. Folding begins centrally and progresses both rostrally (towards the head) and caudally (towards the tail).

An error in neurulation can occur if the neural tube fails to close properly. One example is spina bifida, where gaps remain in the vertebrae and parts of the spinal cord may protrude. If the defect occurs near the top of the spinal cord, the cerebellum can block the fourth ventricle, increasing pressure in the brain and causing malformations or damage. This can lead to symptoms such as cerebellar ataxia, including problems with balance, coordination, and walking.

Explain (briefly) two different mechanisms that migrating neurons and axons use to “find” their way to their correct place in the developing nervous system

One mechanism involves chemical gradients. Developing neurons and axons respond to attractive and repulsive chemical cues released by surrounding cells. By detecting differences in the concentration of these chemicals, growth cones and migrating neurons can move toward some signals and away from others, helping them reach the correct location in the nervous system.

A second mechanism involves interactions with static cellular cues, particularly radial glial cells. Migrating neurons often travel along radial glia, which act like scaffolding to guide them to their final destination in the cortex. Chemical exchanges and cell-adhesion interactions between neurons and glial cells help tell neurons when to continue moving and when to stop migrating.

What determines if a synapse is kept and consolidated or pruned? How might where the synapse is on a neuron influence this?

Whether a synapse is kept and consolidated or pruned depends largely on how active and effective it is. Synapses that successfully activate the postsynaptic cell lead to the exchange of neurotrophic factors, which support survival and strengthen the connection both chemically and structurally. Synapses that are inactive or fail to contribute effectively do not receive this support and are more likely to be eliminated through pruning. This follows the principle that “neurons that fire together wire together.”

The location of a synapse on a neuron can also influence this process. Synapses located far away from the cell body on distal dendrites produce weaker electrical signals by the time they reach the nucleus, whereas synapses closer to the cell body have a stronger influence on whether the neuron fires an action potential. Because stronger and more effective synaptic activity is more likely to stabilise connections, synapse location may affect the likelihood that a synapse is maintained or pruned.

Briefly explain what "regressive growth” means in terms of neural development

“Regressive growth” refers to the normal developmental process in which excess neurons, synapses, and connections are removed to make neural circuits more efficient. Early in development, the brain produces far more synapses and connections than are ultimately needed. For example, children around ages 2–4 have roughly 150% of the synaptic connections seen in adults.

As development continues, weaker or less active connections are pruned through processes such as synaptic elimination and apoptosis. Neurons and synapses that make successful, active connections receive neurotrophic support and survive, while those that do not are removed. This loss of excess connections improves the efficiency and specialization of brain circuits.

How does the thickness of the cortex (mostly) change after middle childhood? Give one reason why this change takes place

After middle childhood, the cortex generally becomes thinner. This reduction in cortical thickness is mainly due to synaptic pruning and other forms of regressive growth that continue through adolescence and into adulthood.

One reason this change occurs is to increase the efficiency of neural circuits. During development, the brain initially forms many more synapses and connections than are needed. Over time, less active or less effective synapses are eliminated, while stronger and more useful connections are maintained. This pruning process helps optimise brain function and improve the efficiency of information processing.

Why is plasticity increased in childhood and why is it useful for an adult brain to have less plasticity than a child's brain?

Plasticity is increased in childhood because many of the genes, molecules, and mechanisms that organise the developing brain are still highly active. Children’s brains are rapidly forming, strengthening, and pruning synapses, allowing neural circuits to be reshaped easily by experience. This high level of plasticity helps children learn quickly, adapt to their environment, and recover more effectively from brain injury.

Lower plasticity in adulthood is useful because adult brain circuits have already been refined and optimised for important everyday functions. Through years of pruning and experience-dependent learning, the brain develops more efficient and stable neural pathways. Although adults learn new skills more slowly, these specialised circuits allow faster and more reliable performance of familiar tasks and prevent constant large-scale changes that could disrupt established functions.

Briefly describe ONE of the following: 1) Experience independent, 2) Experience
dependent or 3) Experience expectant plasticity

Experience-expectant plasticity refers to brain development that depends on receiving common experiences that the brain “expects” to encounter during development. The nervous system is genetically prepared for these experiences, but the experiences themselves are needed to properly shape and stabilise neural circuits.

A good example is the development of sensory systems. Visual and auditory circuits do not fully mature until infants receive sensory input from seeing and hearing the world. Experience helps tune these systems to the specific environment, such as shaping language circuits to recognise the speech sounds that are common in the child’s native language.

What is one brain change that takes place during aging and why does it occur?

One brain change that occurs during aging is a decline in white matter integrity, particularly after around age 50. White matter pathways become less efficient and more vulnerable to damage, which can slow communication between different brain regions and contribute to cognitive decline.

One reason this occurs is the accumulation of cellular damage over time. Factors such as oxidative stress, reduced vascular health, protein accumulation, toxins, and mutations increase cell damage and cell death in the aging brain. These processes can damage myelin and other components of white matter, reducing the efficiency of neural communication.

Briefly explain the role of chaperones in protein folding.

Chaperone proteins help other proteins fold into their correct three-dimensional shape. They guide the folding process, protect proteins from unwanted chemical interactions while folding, and help maintain the proper cellular environment needed for stable protein formation.

Chaperones also help manage misfolded proteins by unfolding them before they are degraded by the proteasome system. This is an important part of the cell’s protein quality control system, which prevents the accumulation of abnormal or aggregated proteins that could damage the cell.

Explain both what "loss of function" effects and "gain of function" effects are in protein aggregation.

“Loss of function” effects occur when misfolded proteins are removed too early or degraded by the cell’s protein quality control system. In this situation, the normal functional protein is no longer available in sufficient amounts, leading to problems because the protein can no longer carry out its usual role in the cell. This can produce a protein deficiency disease.

“Gain of function” effects occur when misfolded proteins are not successfully cleared and instead accumulate inside or outside cells. These abnormal protein aggregates can become toxic, interfere with cellular processes, damage other proteins, and contribute directly to disease pathology. Many neurodegenerative diseases involve this type of toxic protein accumulation.