Neurodevelopment

Question 1

Day 1 of human embryo

Answer 1

Human zygote consists of a single cell.

Question 2

Day 2 of human embryo

Answer 2

This cell divides and continues to divide.

Question 3

Day 15 of human embryo

Answer 3

Emerging embryo is formed by several sheets of cells with a raised area in the middle called an embryonic disc.

Question 4

Day 21 of human embryo

Answer 4

Primitive neural tissue forms the neural plate.

Question 5

What is a neural tube

Answer 5

• Cells in the neural tube are thought of as the nursery for the rest of the CNS!
• Cylinder type space in the neural tube remains open;
• Gives rise to the brain’s ventricles and the spinal canal.

Question 6

Day 49 of human embryo

Answer 6

Embryo resembles a miniature person

Question 7

Day 100 of human embryo

Answer 7

Brain begins to resemble that of a human.

Question 8

7 months of human embryo

Answer 8

Formation of gyri and sulci.

Question 9

9 months of human embryo

Answer 9

Very distinct human brain, although cellular structures is still much different than adult brain.

Question 10

Neural Stem Cells

Answer 10

• Multipotential cell;
• Lining the neural tube;
• Extensive capacity for self renewal;
• In adults, neural stem cells line the ventricles forming the sub ventricular zone;
• Neural stem cells give rise to progenitor cells (aka precursor cells).

Question 11

What can Progenitor be divided into

Answer 11

Neuroblasts

Glioblasts

Question 12

What is Neuroblasts

Answer 12

develop into mature neurons;

Question 13

What is Glioblasts

Answer 13

develop into mature glia.

Question 14

How can we ensure stem cells become mature neurons/glia?

Answer 14

Newborn cells use chemical signals & genetic instructions throughout the
developmental process.
1.Prolactin – naturally occurring hormone that helps replace lost neurons in animal models;
2. Gene transcription – turning on the correct genes that dictate a stem cell will become a neuron and not a skin cell, for example;
3. Epigenetic

Question 15

Neurotrophic Factors

Answer 15

Chemical compounds that act to support growth and differentiation of neurons;

• Keeps adult neurons alive and healthy;
  1. Epidermal Growth Factor (EGF) and Basic Fibroblast Growth Factor (bFGF)

Question 16

What is Basic Fibroblast Growth Factor (bFGF)

Answer 16

stimulates progenitor cells to produce neuroblasts.

Question 17

What is Epidermal Growth Factor (EGF)

Answer 17

stimulates stem cells to produce progenitor cells;

Question 18

What are Neuroblasts

Answer 18

Neuroblasts serve as an all-purpose neuron until they are exposed to certain growth factors in other areas.
These chemical messengers will dictate the fate of the neuron.

Question 19

Neurodevelopmental Stages

Answer 19

1. Cell Birth to neurogenesis, gliogenesis;
2. Cell Migration to traveling to final destination;
3. Cell Differentiation to developing specific tools/skill set;
4. Cell Maturation to dendritic development, axonal growth;
5. Synaptogenesis to formation of synapses;
6. Cell Death to apoptosis/pruning;
7. Myelogenesis to formation of myelin sheath.

Question 20

Neurogenesis

Answer 20

Largely complete by 5 months (prenatally);
During this time, brain is resilient to injuries (i.e. teratogens) and/or trauma;
Note: resilient ≠ resistant.

Question 21

Cell Migration

Answer 21

Begins just after neurogenesis is complete;

Lasts for ~6 weeks.

Question 22

Cell Differentiation

Answer 22

Begins during migration, continues after
migration is complete;
More-or-less complete at time of birth.

Question 23

Cell Maturation

Answer 23

This process occurs for years, well into adulthood; Growth of dendrites and axons;

Question 24

Synaptogenesis

Answer 24

Each neuron begins forming its own networks; Can synapse with hundreds or thousands of other neurons;

Question 25

Cell Death

Answer 25

If you don’t use it, you lose it;

Question 26

Myelogenesis

Answer 26

Neuronal networks become more efficient in their communication;
Sign of neurodevelopmental maturity; Occurs well into adulthood;

Question 27

Subventricular Zone (SVZ)

Answer 27

• SVZ contains a primitive map of the cerebral cortex;

- Cells formed in certain regions of the SVZ migrate to certain cortical locations.

Question 28

Radial Glial Cells

Answer 28

• Form a path that extends from the SVZ to the surface of the cortex;
• Undifferentiated progenitor cells follow this path.

Cortical layers form from inside out. The most inner layer (VI) are first to form.
Q: How do neurons know when to stop? (i.e. cortical thickness)

Question 29

How do cells get to their final destination?

Answer 29

Intercellular signals (i.e. between cells) progressively restrict the choice of traits a cell can express.
Therefore, the emergence of a cell type is a combination of genetic instructions, timing and signals from neighboring cells in the local environment.

Question 30

A maturing neurons needs:

Answer 30

1. Dendritestoprovidesurfacearea for synapse formation:
   - Branching of dendrites (arborization); - Growth of dendritic spines (μm.day-1).
2. Axon extending to appropriate target to initiate synapse formation
   - Occurs very rapidly (mm.day-1);
   - Various molecules attract or repel axon tip, thus guiding it through a very complex terrain.

Question 31

Growth Cones

Answer 31

Santiago Ramón y Cajal defined growing axons as growth cones.

Question 32

Filopod

Answer 32

Growth cones extend shoots called filopod (e.g. fingers on a hand);
When filopod reaches an appropriate target, the others follow.

Question 33

Growth cones are responsive to:

Answer 33

1. Cell-adhesion Molecules (CAMs) Secreted from cells or lie on cell surface.
2. Tropic Molecules
   Secreted from target cells;
   Carry “come here” or “go away” message; Netrin (L. to guide) is the only known group.

Question 34

Synaptic Development

Answer 34

Human brain contains about 1014 synapses;

• The amount and array of synaptic connections is thought to be guided mostly by environmental cues and signals;
• At 7th gestational months, these connections are rather simple;
• At birth, the number of synapses increases dramatically;
• By 2 – 4 months, the number of synapses in the visual cortex doubles, and continues to increase for years.

Question 35

Synaptic Pruning

Answer 35

The brain uses apoptosis as a method of pruning
- Genetics signals, experience, hormones, stress, etc. are all factors that can initiate apoptosis;
- ~42% of all synapses in human cortex are lost.
Neural Darwinism
- Competition drives neuronal loss;
- Environmental pressure leads to competition amongst neurons.

Question 36

Nerve Growth Factor (NGF)

Answer 36

is a neurotrophic factor produced by cells that regulate neuronal survival;

• Therefore, neurons that are deprived of NGF will undergo apoptosis;
• Those neurons who make connections early on will be nourished with NGF and other growth factors.

Generally, the cortex continues to thin from ages 5 to 20
The exception to this is in language centers
- Unique role of language processing and nature of language-learning processes makes this area an exception to this rule.

Question 37

Myelination

Answer 37

Frontal lobe is the last brain region to mature
- Pruning occurs into the 20’s
Process of myelination can be used as an index of neuronal maturity.
Early-myelinating areas control simple movement, while late-myelinating areas control highest mental function.

Question 38

Experience & Cortical Organization

Answer 38

Donald Hebb (1947)

• Took some laboratory rats home and let them grow up in his kitchen;
• Control group stayed at McGill University;
• The ‘home’ rats had many more experiences then the ‘cage’ rats;
• On subsequent intelligence tests, the home rats outperformed the cage rats;
• Hebb concluded that experience must influence intelligence in some way;
• Hebb’s experiment lead to the development of Sesame Street which aimed to offer enrichment for children.

Question 39

Experience & Cortical Organization

Answer 39

Stimulation is extremely important during development and cortical organization

• Tactile stimulation has been shown to increase the growth rate of pre-mature babies in an incubator;
• Brushing infant rats for 15 minutes 3 times daily speeds up growth and development;
• Tactile stimulation of infants is important for forming bond with caregiver;
• Experience changes structure of neurons, especially cortical neurons;
• Processing of sensory information increases number of synapses and astrocytes.

Question 40

Abnormal Experience & Brain Development

Answer 40

Donald Hebb (1951), Sensory Deprivation Studies

• Placed Scottish terrier in the dark with as little stimulation as possible and compared them to ‘normal’ dogs;
• Later in life, deprived dogs didn’t pay attention to other dogs or humans;
• Lost sensation of pain;
• Performed very poorly on intelligence test;
• Depriving young animals of visual input or maternal contact has devastating; consequences on behavioral development (and presumably brain development).

Question 41

Abnormal Experience & Brain Development

Answer 41

Austin Riesen (1982)
- Extensively studied animals raised in the dark;
- Atrophy of dendrites in visual cortex, which is the opposite of what happened to the enriched rats;
- Eye still worked, but functionally blind.
Harry Harlow (1950’s)
- Monkeys raised with no maternal/paternal contact showed abnormal intellectual and social behaviors in adulthood;
- There are a number of hormonal and neurobiological abnormalities among motherless monkeys.
Romanian Orphans (1970’s)
- Birth control & abortions were outlawed;
- Fed and clothed, but virtually no environmental stimulation;
- Motor and cognitive impairments;
- Age of adoption dictated extent of recovery.