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Medsci 317 > Lecture 9; Structural and functional brain development > Flashcards

Lecture 9; Structural and functional brain development Flashcards

1
Q

What are the key processes of prenatal brain development?

A
  • Development form the neural tube
  • Neural proliferation, migration, differentiation, Axon/dendritic outgrowth, synapse formation, pruning, programmed cell death
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2
Q

Describe the brain cells and briefly describe why structure exists

A
  • 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
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3
Q

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

A

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

i.e motor function improves during childhood

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4
Q

When does the most significant brain weight gain occur?

A

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

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5
Q

What are critical time points in development?

A

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

Brain growth only slows after one year

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6
Q

Describe the timing of major events in brain development

A

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

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7
Q

What drives the refinement of neural structures?

A

Pruning is driven by environmental input

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8
Q

Describe embryonic disc

A

Fetilisation leads to the formation of a 3 layered embryonic disc

  • Endoderm
  • Mesoderm
  • Ectoderm (CNS)
  • Initial CNS development termed neuralation
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9
Q

Describe neural tube development;

A

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

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10
Q

Describe neural tube differentiation;

A

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
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11
Q

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

A

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
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12
Q

What does each neural tube vesicle form?

A 
Telecephalon = cerebellum
Diancephalon = thalamus, hypothalamus, epithalamus
Mesencephalon = mid brain
Metencephalon = pons + cerebellum
Myeloncephalon = medulla oblongata
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13
Q

What is unique about the cerebral ventricles?

A

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

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14
Q

Describe cerebral ventricle formation;

A

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

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15
Q

Describe the histogenesis of of CNS cells;

A

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.

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16
Q

Whats important regarding the timing of cell genesis;

A

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.

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17
Q

Describe the timing of cell genesis and events

A

Proliferation

neurogenesis and migration

Glialgenesis and maturation

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18
Q

Whats an important structural event that occurs during development?

A

Brian folding and development of the cerebral cortex

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19
Q

Describe cortical GM volume and post concenptional age;

A

Rapid change in volume over time therefore susceptible to damage

20
Q

Describe the layers of the neocortex;

A

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

21
Q

What happens to the sub plate?

A

Disappears post birth

Important for cortical development and circuit development in the thalamus

22
Q

Describe cortical layers and their relationship with time;

A
  • 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

23
Q

When does neural migration primarily occur?

A

8-20 weeks of gestation

completed mostly by 25-29 weeks

24
Q

What are the types of neural migration?

A

Passive migration (cell displacement)

Active migration

25
Q

Describe the features of passive migration;

A
  • Oldest cells are located farthest away from proliferation zone
  • Short distances
  • i.e thalamus, dentate gyrus, brain stem
26
Q

Describe the features of active migration;

A
  • 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
27
Q

Describe active neural migration;

A
  • 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
28
Q

What are the two main modes of active migration;

A

Radial and tangential migration

29
Q

Describe where radial glial migration occurs;

A
  • neuroblasts move from ventricular/subventricular zones to CC (90%) via radial glial cells
30
Q

Describe where tangential (parallel) migration occurs

A
  • GABAergic interneurons migrate from medial and lateral ganglion eminances into the cortex
  • last cells in cortex 18-36 weeks

These produce oligiodendrocytes too

31
Q

When does neural differentiation occur?

A
  • Neuroblasts have simple morphology
  • Begin to differentiate during migration and once they reach their destination

25 weeks till adolescence

32
Q

What are the overlapping events of neural differentiation?

A
  • 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
33
Q

When is dendritic development the greatest?

A

32 weeks -> birth

Continues into adolescence

34
Q

What guides axon growth?

A

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

35
Q

Describe axon growth;

A

•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

36
Q

Describe synaptogenesis

A
  • 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!

37
Q

What is one of the last events of neural development?

A

The development of specific neurochemical circuits / systems

38
Q

What is the function of neural circuits?

A

•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

39
Q

What are the two key pathways in the brain?

A

–Thalamocortical(TC; connecting thalamus to cortex) (sensory)

–Corticothalamic(CT; connecting cortex to thalamus) (motor)

40
Q

How do these pathways function?

A

•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

41
Q

When do CT / TC pathways develop?

A

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

42
Q

What is the subplate?

A

Subplate

– thick transient layer of neurons during fetal life

–Plays a critical role in formation of TC pathway

43
Q

Describe TC connectivity and the subplate;

A

~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)

44
Q

What happens 24-30 weeks regarding the sub plate?

A

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

45
Q

Is the SP present at term?

A

•SP neuron apoptosis, and SP largely disappears by term

46
Q

What does the sub plate essentially do?

A

Helps create circuits to the thalamus

47
Q

Why is there apoptosis in neural development?

A

•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

Medsci 317 (32 decks)

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