Lecture 9; Structural and functional brain development

Question 1

What are the key processes of prenatal brain development?

Answer 1

• Development form the neural tube
• Neural proliferation, migration, differentiation, Axon/dendritic outgrowth, synapse formation, pruning, programmed cell death

Question 2

Describe the brain cells and briefly describe why structure exists

Answer 2

• 10-20billion neurons
• 50-200 billion glial cells (oligiodendrocytes, astrocytes, microglia etc)
• Each division and sub division of brain has its own structure and function
• Each portion and structure of CNS is intergrated into a whole to allow coherent functioning

Question 3

What do lots of events during the prenatal development stage focus on doing?

Answer 3

Lots of events during the perinatal period are focus on circuit development and brain functionality

i.e motor function improves during childhood

Question 4

When does the most significant brain weight gain occur?

Answer 4

The most rapid period of brain weight gain occurs before and immediately after 40 weeks of gestation

Question 5

What are critical time points in development?

Answer 5

0-3 months = emergence of cognitive circuits
0-15 months = maturation of cognitive events

Brain growth only slows after one year

Question 6

Describe the timing of major events in brain development

Answer 6

1) Cell birth, neurogenesis (ends ~18 weeks)
2) Migration, ~24 weeks is complete, structures formed
3) Axonal/dendritic outgrowth / glial formation
4) Programmed cell death
5) Synaptic formation
6) Myelination
7) Synaptic elimination / pruning

Question 7

What drives the refinement of neural structures?

Answer 7

Pruning is driven by environmental input

Question 8

Describe embryonic disc

Answer 8

Fetilisation leads to the formation of a 3 layered embryonic disc

• Endoderm
• Mesoderm
• Ectoderm (CNS)
• Initial CNS development termed neuralation

Question 9

Describe neural tube development;

Answer 9

2-3 weeks after conception

Neural crest cells come together to form neural tube (neuralation)

1- Neural plate
2- Neural groove
3- Neural crest
4- Neural tube

Question 10

Describe neural tube differentiation;

Answer 10

Precursor neural tissue cells in neural tube are called neural epithelial cells.

This rapidly proliferate and differentiate in radial, circumferential and longitudinal directions at 4-5 weeks

• main driver of brain growth
• Vesicle formation

Question 11

Describe the difference in structure between neural tube week 3 and vesicle formation at week 5

Answer 11

week 3-4 (3 vesicles)

• Prosencephalon
• mesancephalon
• rhombancephalon

week 5-7

• (Prosencephalon is now) Telecephalon (x2) and Diancephalon
• mesencephalon is unchanged
• rhombancephalon is now) metencephalon and myeloncephalon

Question 12

What does each neural tube vesicle form?

Answer 12

Telecephalon = cerebellum
Diancephalon = thalamus, hypothalamus, epithalamus
Mesencephalon = mid brain
Metencephalon = pons + cerebellum
Myeloncephalon = medulla oblongata

Question 13

What is unique about the cerebral ventricles?

Answer 13

Sub ventricular and ventricular zones are the sites of neurogenesis

Giving rise to neuroblasts that will go out and form the cerebral cortex (neurons and glia)

up to 250,00/min

Question 14

Describe cerebral ventricle formation;

Answer 14

Cavity within the neural tube forms the ventricles of the brain and central canals of the spinal cord

Question 15

Describe the histogenesis of of CNS cells;

Answer 15

Neuroepithelium forms neurons and glial cells

Mesenchymal cells migrate to the brain and form microglail cells which form ependymall cells

Ependymal cells formed by the neuroepithelium and mesenchymall cells give rise to the cells of the choroid plexus.

Question 16

Whats important regarding the timing of cell genesis;

Answer 16

Depending on the time of development, insults to the feotus can vary in magnitude, but tend to be bad during brain development as this occurs so rapidly.

Question 17

Describe the timing of cell genesis and events

Answer 17

Proliferation

neurogenesis and migration

Glialgenesis and maturation

Question 18

Whats an important structural event that occurs during development?

Answer 18

Brian folding and development of the cerebral cortex

Question 19

Describe cortical GM volume and post concenptional age;

Answer 19

Rapid change in volume over time therefore susceptible to damage

Question 20

Describe the layers of the neocortex;

Answer 20

1) Molecular zone
2) Cortical plate (layers 2-6)
3) Subplate (Dissapears post birth)
4) Intermediate zone
5) Sub ventricular zone
6) Ventricular zone

Question 21

What happens to the sub plate?

Answer 21

Disappears post birth

Important for cortical development and circuit development in the thalamus

Question 22

Describe cortical layers and their relationship with time;

Answer 22

• 4 weeks, the ventricular zone and preplate are formed
• Pre plate is the first evidence of the cerebral cortex
• 6 weeks the ventricular one divides into the sub ventricular zone and ventricular zone, preplate thickness increases
• 7 weeks preplate splits into ; Cortical plate (& molecular zone) and subplate / intermediate zone

Cortical plate becomes layers 2-6 of cerebral cortex

Question 23

When does neural migration primarily occur?

Answer 23

8-20 weeks of gestation

completed mostly by 25-29 weeks

Question 24

What are the types of neural migration?

Answer 24

Passive migration (cell displacement)

Active migration

Question 25

Describe the features of passive migration;

Answer 25

- Oldest cells are located farthest away from proliferation zone - Short distances - i.e thalamus, dentate gyrus, brain stem

Question 26

Describe the features of active migration;

Answer 26

- Movement of younger cells past older cells (inside out) Migrate up radial glial cells from cortical layers 6-1 - Long distances - i.e Cerebral cortex

Question 27

Describe active neural migration;

Answer 27

- Neuroblasts migrate up radial glial cells following diffusive chemical signal gradient. - Neuroblasts propels itself using actin filaments - It knowns when it has reached its destination and response to a signal and hops off and is deposited in the cortical layer, here it aggregates and starts forming structures

Question 28

What are the two main modes of active migration;

Answer 28

Radial and tangential migration

Question 29

Describe where radial glial migration occurs;

Answer 29

- neuroblasts move from ventricular/subventricular zones to CC (90%) via radial glial cells

Question 30

Describe where tangential (parallel) migration occurs

Answer 30

- GABAergic interneurons migrate from medial and lateral ganglion eminances into the cortex - last cells in cortex 18-36 weeks These produce oligiodendrocytes too

Question 31

When does neural differentiation occur?

Answer 31

- Neuroblasts have simple morphology - Begin to differentiate during migration and once they reach their destination 25 weeks till adolescence

Question 32

What are the overlapping events of neural differentiation?

Answer 32

* Dendritic growth/arborization (post-synaptic connections with axons of other neurons) * Axonal growth and targeting (short and long range fiber pathways) * Synapse formation (synaptogenesis) * Neurotransmitter receptor expression

Question 33

When is dendritic development the greatest?

Answer 33

32 weeks -> birth Continues into adolescence

Question 34

What guides axon growth?

Answer 34

•Short/long range axon guidance –Guidance cues (fixed or diffusible chemical) –Attract or repel –Netrins, Slits (secreted), Ephrins, Semaphorins (cell surface)

Question 35

Describe axon growth;

Answer 35

•Highly motile growth cone (detects cues in ECM) –Dynamic extension of developing axon –Contains sensory, motor, integrative and adaptive functions required for axonal growth and targeting

Question 36

Describe synaptogenesis

Answer 36

* Axons (with growth cones on end) and dendrites form a synapse with other neurons or tissue (e.g. muscle) * Neurobiological substrate of almost all cell-cell communication –Each neuron forms thousands of synapses –~28 weeks – 2- 3 years ~40,000 synapses per second!

Question 37

What is one of the last events of neural development?

Answer 37

The development of specific neurochemical circuits / systems

Question 38

What is the function of neural circuits?

Answer 38

•For normal brain function, brain structures are connected into circuits –Set of integrated components that serve a specific function –Cognition, emotions and behavior all controlled by brain circuits –Circuit formation started prenatally circuit development occurs prior to birth All the main circuits involve the thalamus

Question 39

What are the two key pathways in the brain?

Answer 39

–Thalamocortical(TC; connecting thalamus to cortex) (sensory) –Corticothalamic(CT; connecting cortex to thalamus) (motor)

Question 40

How do these pathways function?

Answer 40

•Transmit sensorimotor information –TC relays sensory and motor information from receptors in retina, cochlea, muscle, or skin to the thalamus and cortex –CT completes feedback loop by transmitting information back to thalamus

Question 41

When do CT / TC pathways develop?

Answer 41

TC/CT pathways develop in second trimester in humans –Main neurogenic event in the late fetal period –Creates a structural substrate for various sensory experiences

Question 42

What is the subplate?

Answer 42

Subplate – thick transient layer of neurons during fetal life –Plays a critical role in formation of TC pathway

Question 43

Describe TC connectivity and the subplate;

Answer 43

~22 weeks: Afferent fibers growing from thalamus initially synapse with SP neurons –Waiting zone until neuronal migration to higher cortical layers complete (still active cortical circuit)

Question 44

What happens 24-30 weeks regarding the sub plate?

Answer 44

~24-30 weeks onwards weeks, axons break connections with SP and form new connections (synapses) with final targets (L4) in overlying cortex

Question 45

Is the SP present at term?

Answer 45

•SP neuron apoptosis, and SP largely disappears by term

Question 46

What does the sub plate essentially do?

Answer 46

Helps create circuits to the thalamus

Question 47

Why is there apoptosis in neural development?

Answer 47

•During proliferation, number of neurons created exceeds that needed in the mature CNS – Some cells must be removed! –~50-70% of neurons produced during neurogenesis die by apoptosis after migration –Neurons die due to failure to compete for chemicals produced at synaptic sites (neurotrophins) – ‘Use it or lose it’ Non inflammatory process