Lecture 9; Structural and functional brain development Flashcards
What are the key processes of prenatal brain development?
- Development form the neural tube
- Neural proliferation, migration, differentiation, Axon/dendritic outgrowth, synapse formation, pruning, programmed cell death
Describe the brain cells and briefly describe why structure exists
- 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
What do lots of events during the prenatal development stage focus on doing?
Lots of events during the perinatal period are focus on circuit development and brain functionality
i.e motor function improves during childhood
When does the most significant brain weight gain occur?
The most rapid period of brain weight gain occurs before and immediately after 40 weeks of gestation
What are critical time points in development?
0-3 months = emergence of cognitive circuits
0-15 months = maturation of cognitive events
Brain growth only slows after one year
Describe the timing of major events in brain development
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
What drives the refinement of neural structures?
Pruning is driven by environmental input
Describe embryonic disc
Fetilisation leads to the formation of a 3 layered embryonic disc
- Endoderm
- Mesoderm
- Ectoderm (CNS)
- Initial CNS development termed neuralation
Describe neural tube development;
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
Describe neural tube differentiation;
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
Describe the difference in structure between neural tube week 3 and vesicle formation at week 5
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
What does each neural tube vesicle form?
Telecephalon = cerebellum Diancephalon = thalamus, hypothalamus, epithalamus Mesencephalon = mid brain Metencephalon = pons + cerebellum Myeloncephalon = medulla oblongata
What is unique about the cerebral ventricles?
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
Describe cerebral ventricle formation;
Cavity within the neural tube forms the ventricles of the brain and central canals of the spinal cord
Describe the histogenesis of of CNS cells;
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.
Whats important regarding the timing of cell genesis;
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.
Describe the timing of cell genesis and events
Proliferation
neurogenesis and migration
Glialgenesis and maturation
Whats an important structural event that occurs during development?
Brian folding and development of the cerebral cortex
Describe cortical GM volume and post concenptional age;
Rapid change in volume over time therefore susceptible to damage
Describe the layers of the neocortex;
1) Molecular zone
2) Cortical plate (layers 2-6)
3) Subplate (Dissapears post birth)
4) Intermediate zone
5) Sub ventricular zone
6) Ventricular zone
What happens to the sub plate?
Disappears post birth
Important for cortical development and circuit development in the thalamus
Describe cortical layers and their relationship with time;
- 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
When does neural migration primarily occur?
8-20 weeks of gestation
completed mostly by 25-29 weeks
What are the types of neural migration?
Passive migration (cell displacement)
Active migration
Describe the features of passive migration;
- Oldest cells are located farthest away from proliferation zone
- Short distances
- i.e thalamus, dentate gyrus, brain stem
Describe the features of active migration;
- 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
Describe active neural migration;
- 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
What are the two main modes of active migration;
Radial and tangential migration
Describe where radial glial migration occurs;
- neuroblasts move from ventricular/subventricular zones to CC (90%) via radial glial cells
Describe where tangential (parallel) migration occurs
- GABAergic interneurons migrate from medial and lateral ganglion eminances into the cortex
- last cells in cortex 18-36 weeks
These produce oligiodendrocytes too
When does neural differentiation occur?
- Neuroblasts have simple morphology
- Begin to differentiate during migration and once they reach their destination
25 weeks till adolescence
What are the overlapping events of neural differentiation?
- 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
When is dendritic development the greatest?
32 weeks -> birth
Continues into adolescence
What guides axon growth?
•Short/long range axon guidance
–Guidance cues (fixed or diffusible chemical)
–Attract or repel
–Netrins, Slits (secreted), Ephrins, Semaphorins (cell surface)
Describe axon growth;
•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
Describe synaptogenesis
- 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!
What is one of the last events of neural development?
The development of specific neurochemical circuits / systems
What is the function of neural circuits?
•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
What are the two key pathways in the brain?
–Thalamocortical(TC; connecting thalamus to cortex) (sensory)
–Corticothalamic(CT; connecting cortex to thalamus) (motor)
How do these pathways function?
•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
When do CT / TC pathways develop?
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
What is the subplate?
Subplate
– thick transient layer of neurons during fetal life
–Plays a critical role in formation of TC pathway
Describe TC connectivity and the subplate;
~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)
What happens 24-30 weeks regarding the sub plate?
~24-30 weeks onwards weeks, axons break connections with SP and form new connections (synapses) with final targets (L4) in overlying cortex
Is the SP present at term?
•SP neuron apoptosis, and SP largely disappears by term
What does the sub plate essentially do?
Helps create circuits to the thalamus
Why is there apoptosis in neural development?
•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
