1. Chapter Five Development of the Human Brain
Sperm trying to merge with an egg
We will talk today about evolution of the brain, and how the brain develops in individuals
Used to think concern about what pregnant women ingest was odd, even exaggerated, but no more, b/c entire system depends on a very delicate balance of chemicals which tell system how to grow and connect

2. Prenatal Development

3. Early Differentiation
Within the first week following conception, the human embryo has divided into three germ layers:
Ectoderm
Mesoderm
Endoderm
Inducing factors
Chemicals which differentiate the ectoderm layer into skin and nervous tissue.
Ectoderm – turns into nervous system, skin, fur, hair, horn
Mesoderm – connective tissue, muscles, blood vessels, bone, urogenital system
Endoderm – internal organs, like stomach and intestines

4. The Closing of the Neural Tube
Start out with a flat plate with the three germ layers
Ecto-outer
meso- middle
Endo- inner
During 3rd week, cells in ectoderm differentiate into new layer, called neural plate
Over time, as more cells formed, plate starts forming groove and then closes, creating a tube
The neural tube will be retained in the mature brain as the ventricle system and central canal of the spinal cord.
Notochord will become vertebrae surrounding spinal cord
notochord

5. Overview of Neural Development
Neurogenesis
Migration
Differentiation
Synaptogenesis
Apoptosis & Myelination
Refinement of synapses
Basic stages, new cells continue to form, they migrate to where they need to be, they differentiate into different cell types, connections formed between neurons, unused cells die, connections fine-tuned

6. 1. Neurogenesis and 2. Migration
Ventricular zone:
A layer of cells that line the inside of the neural tube, creates new neurons
Some daughter cells remain in the ventricular zone and continue to divide.
Other daughter cells migrate away from the ventricular zone along radial glia.
Ventricular zone
contains founder cells that divide and give rise to the central nervous system.
New neural cells are produced in the ventricular zone lining the neural tube.

7. 1. Neurogenesis After7th week, Show cells remaining, cells migrating
Height of neurogenesis, up to 250,000 new cells per minute

8. 2. Migration 11 weeks Radial glial cells provide ladder
About 2/3rds of cells migrate up, 1/3 horizontally
They will eventually form the six layers of cortex

9. Resulting Cortical Layers
Layers II and IV small neurons, get info
Layers III and IV large neurons, project info out
Process is inside out
Cells that end up on bottom layers form first, then next layers, etc.
Which means that upper layers have to migrate thru lower layers (think of it like building a building, first floor supports first, then have to haul materials for next floors after that)

10. 3. Differentiation Daughter cells differentiate into neurons or glia.
The neural tube differentiates in two directions:
between the dorsal and ventral halves.
along the rostral-caudal axis.
Both genes (producing chemicals) and different types of input can be responsible for differentiation
The neural tube differentiates in two directions:
between the dorsal and ventral halves - from posterior end of spinal cord up to midbrain, dorsal is sensory, ventral is motor
Ex. substantia nigra is in ventral part of hindbrain, important for motor control, superior colliculus is eye reflexes, sensory
Sonic hedgehog (released by notochord) is protein signal for ventral, BMP (bone morphogenetic protein) for dorsal.
along the rostral-caudal axis – similar thing happens with chemicals/genes/input

11. 3. Differentiation The developing brain
So here’s the rostral – caudal differentiation,
Top pictures looking from a dorsal view, bottom from sagittal view
Copyright © 2004 Allyn and Bacon

12. 4. Synaptogenesis The Growth Cone
Once neurons are in the right place they have to connect up to each other
Process starts by having axon from cell form a growth cone, sort of like an ameoba, extensions formed that spread out,
Extensions stick to certain places and avoid other places, which is controlled by guidepost cells
As axon grows, microtubules form to hold structure in place
From Bridgman, P.C. and Dailey, M.E., “The organization
of myosin and actin in rapid frozen nerve growth cones,”
Journal of Cell Biology, 108, pp. 95–109

13. Growth Cones Respond to External Cues
Growing axon adheres to:
Certain cells
Other axons
Guidepost cells (which release attracting chemical)
Avoid of guidepost cells (which release repulsing chemicals)
Once processes in general correct area, connections are refined thru experience

14. A Synapse Is Formed
Synapse forming a neuromuscular junction, place where motor neuron axon connects to muscles
Growth cone approaches, makes contact, forms synapse
In muscles, originally receptors locating evening throughout muscle, when synapse formed, receptors cluster where synapse is
The identity of a cell's major neurotransmitter substance appears to be influenced by the postsynaptic neuron

15. 5. Apoptosis
Significant numbers of new neurons die during the development process.
Neurons appear to compete for nerve growth factors (NGF), and those that fail to obtain this stimulation die.
Synapses follow a similar pattern of overproduction followed by "pruning."
Apoptosis comes from word meaing “falling leaves”
Target cells release NGF, but have only a limited supply, not enough to support all available cells
Cell automatically dies if it doesn’t get enough NGF
Why would system bother creating and then killing so many cells?
Having a lot of cells helps system be flexible
But too many cells in the end may cause autism or retardation

16. Visual Synapses Peak at 1 Year of Age
We may lose as much as 42% of synapses in first year

17. 5. Myelination
Myelination occurs from the spinal cord rostrally towards the forebrain.
Sensory systems are myelinated before motor systems.
Although the majority of myelination occurs very early in childhood, human myelination is not complete until about the age of 20 years.

18. Experience Affects Development
Plasticity
Ability of nervous system to change
Critical period
Segment of time during development in which experience can change system; after this time, experience causes little or no change in system
Plasticity – in adults usually just means changing strength of synapses, younger could be more extensive structural changes
Some systems have very definite time period duirng which they can change, and then after that they have no ability to change
Examples of systems with critical windows:
Vision
Language
Effects of an enriched environment
Imprinting
Language, able to utter all sounds when we are born, but gradually only use ones in language that we hear

19. Input Organizes the LGN
Target cell in LGN (part of the thalamus, part of visual system) originally gets input from three cells, one from left eye, two from right eye
Left eye axon releases some NT, but not enough to cause AP in LGN cell
Right eye axons are stimuluated and release more NT, which does cause AP,
Synapses for right get stronger, left eye weaker, and more terminals from right eye take its place

20. Disorders of Development
As the neural tube closes early in development, mistakes may occur, leading to spina bifida and anencephaly.
Genetic disorders affecting development include trisomy 21, or Down syndrome, fragile X and phenylketonuria.
Environmental toxins, including alcohol, tobacco and other legal and illegal substances, can interfere with the normal course of development.

21. Courtesy Dr. Sterling K. Clarren
Fetal Alcohol Syndrome May Produce Physical and Intellectual Abnormalities
Developing brain cells and structures are underdeveloped or malformed by prenatal alcohol exposure,
creating an array of primary cognitive and functional disabilities (including poor memory, attention deficits, impulsive behavior, and poor cause-effect reasoning) as well as secondary disabilities (for example, mental health problems, and drug addiction)
first trimester - interferes with migration and organization of brain cells, which can create structural deformities or deficits within the brain.
third trimester, damage can be caused to the hippocampus, which plays a role in memory, learning, emotion, and encoding visual and auditory information, all of which can create neurological and functional CNS impairments as well
Courtesy Dr. Sterling K. Clarren