Mechanisms of Neural Development

Question 1

What are the 4 stages in neural development?

Answer 1

1. Neurogenesis; creating the right number of neurons
2. Migration and Differentiation; getting right cells to the right place
3. Axon guidance and Synaptogenesis; making connections with useful partners
4. Activity-dependent refinement; testing and perfection of neural circuit

Question 2

Neurogenesis:
What gives rise to the nervous system?

In which arrangement do the Neuroepithial (glial) cells form as they divide?

What can it lead to if these cells divide too many/few times?

What does the parallel division of the Neuroepithial cells produce in the daughter cells? What does this allow for?

Answer 2

• ECTODERM
• Form between the Pial cells (outer surface) and luminal (ventricular) surface; as cells divide perpendicularly, they increase the surface area
• Primary Microcephaly or Macrocephaly
• Morphogen gradient in the daughter cells; allows for differentiation into Neuroblast cells

Question 3

Migration and Differentiation:
What drives cell differentiation?

What tells the cells where to go?

Where do the cells formed in the cerebrum area migrate? Excitatory or Inhibitory?

Where do the cells formed at the front go? Excitatory or Inhibitory?

Which cells are produced first and second by the cerebral cortex?

Describe the projections of the 3 cortical plate layers?

What does a loss of Reelin lead to?

What does a loss of Doublecortin lead to?

Answer 3

• MORPHOGENS
• Guidance chemicals
• Migrate upwards towards the Reelin, which is produced on the Pia surface; EXCITATORY
• Can stay to become basal ganglia cells or migrate upwards into the cerebral hemispheres; INHIBITORY
• First are Subplate cells that die-off before birth, Second are the Cortical Plate cells
• • Deep layers project into subcortical structures
  • Middle layers receive from subcortical and cortical inputs
  • Superficial layers project into other cortical areas
• LISSENCEPHALY; severe learning difficulties and seizures
• Heterotopia; loss of cortex layer organisation

Question 4

Axon guidance:
What do the growing tips of neurites consist of?

What are the types of guidance signals and what do they cause?

Synaptogenesis:
What are the stages by which an axon tries to find a useful cell to synapse with?

Answer 4

• Filopodia (supported by actin bundles) and Lamellipodium (supported by actin meshwork)
• • Attractive guidance signals cause actin bundles to grow
  • Repulsive guidance signals cause actin bundles to shrink
• 1. Filopodia extend from dendrites, seeking contact from passing axons
     
     2. Complementary surface proteins bind, triggering the formation of a synapse
     3. Filopodia retracts if there are no complementary binding molecules

Question 5

Activity-Dependant Refinement:
What does the strengthing/weakening of a synapse depend on?

What occurs during the activation of a single synapse compared to a large circuit of synapses?

What do the NMDA receptors do?

Answer 5

• How much it’s being used
• Activation of AMPA receptors (for Na+) at single synapse produces little depolarisation; NMDA (for Ca2+) receptors remain blocked by Mg2+
  o If synapse is part of an effective circuit, many synapses will activate simultaneously, causing full depolarisation; NMDA receptors will open
• Allows Ca2+ entry = triggers processes that strengthen the synapses
  o ↑AMPA receptors
  o ↑Neurotransmitter release

Question 6

Synaptic plasticity:
Who is it effective in? Why?

Why is it important to correct the problem as quickly as possible?

How does plasticity change over time?

Answer 6

• Effective in foetus and babies; babies who suffer severe brain injuries can recover a lot of lost function
• Its pathway will become fixed and adapted to the situation
• Plasticity decreases with age, and wiring of major pathways become permanent