Development and Maturation of

the
Vertebrate Brain.
Lecture 2.
Annum Tanweer.
Context: Kalat, chapter 5. 1
• The human central nervous system begins to form when the embryo
is about 2 weeks old.
• The dorsal surface thickens forming a neural tube surrounding a fluid
filled cavity.
• The forward end enlarges and differentiates into the hindbrain,
midbrain, and forebrain.
• The rest of the neural tube becomes the spinal cord
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• Originally believed that no new neurons were formed after early
development.
• Later research suggests otherwise:
• Stem cells are undifferentiated cells found in the interior of the brain that
generate “daughter cells” that can transform into glia or neurons.
• New olfactory receptors also continually replace dying ones.
• Development of new neurons also occurs in other brain regions; Example:
songbirds have a steady replacement of new neurons in the singing area of
the brain.
• Stem cells differentiate into new neurons in the adult hippocampus of
mammals and facilitate learning.
• The fluid-filled cavity becomes the central canal of the spinal cord and
the four ventricles of the brain. The fluid is the cerebrospinal fluid.
• At birth, the human brain weighs approximately 350 grams.
• By the first year, the brain weighs approximately 1000 grams.
• The adult brain weighs grams 1200-1400 grms
• The development of neurons in the brain involves the following
processes:
• Proliferation
• Migration
• Differentiation
• Myelination
• Synaptogenesis
Proliferation
• Proliferation refers to the production of new cells/ neurons in the
brain primarily occurring early in life.
• Early in development, the cells lining the ventricles divide.
• Some cells become stem cells that continue to divide.
• Others remain where they are or become neurons or glia that migrate
to other location
Migration
• Migration refers to the movement of the newly formed neurons and
glia to their eventual locations.
• Some don’t reach their destinations until adulthood.
• Occurs in a variety of directions throughout the brain.
• Occurs via cells following chemical paths in the brain of
immunoglobins and chemokines.
Immunoglobulins and cytokines
• deficit in these chemicals leads to impaired migration, decreased
brain size, decreased axon growth, and mental retardation.

• excesses of immunoglobulins have been linked to some cases of

schizophrenia.
Differentiation
• Differentiation refers to the forming of the axon and dendrite that
gives the neuron its distinctive shape.
• The axon grows first either during migration or once it has reached its
target and is followed by the development of the dendrites
Myelination
• Myelination refers to process by which glia produce the fatty sheath
that covers the axons of some neurons.
• Myelin speeds up the transmission of neural impulses.
• First occurs in the spinal cord and then in the hindbrain, midbrain and
forebrain.
• Occurs gradually for decade
Synaptogenesis
• Synaptogenesis is the final stage of neural development and refers to
the formation of the synapses between neurons.
• Occurs throughout the life as neurons are constantly forming new
connections and discarding old ones.
• Slows significantly later in the lifetime
Pathfinding by Axons
• Axons must travel great distances across the brain to form the correct
connections.
• Sperry’s (1954) research with newts indicated that axons follow a
chemical trial to reach their appropriate target.
• Growing axons reach their target area by following a gradient of
chemicals in which they are attracted by some chemicals and repelled
by others
• When axons initially reach their targets, they form synapses with
several cells.
• Postsynaptic cells strengthen connection with some cells and
eliminate connections with others.
• The formation or elimination of these connections depends upon
input from incoming of axons.
• Some theorists refer to the idea of the selection process of neural
connections as neural Darwinism. In this competition amongst
synaptic connections, we initially form more connections than we
need. The most successful axon connections and combinations
survive while the others fail to sustain active synapses
Determinants of Neuronal Survival
• Levi-Montalcini discovered that muscles do not determine how many
axons form; they determine how many survive.
• Nerve growth factor (NGF) is a type of protein released by muscles
that promotes the survival and growth of axons.
• The brain’s system of overproducing neurons and then applying
apoptosis enables the exact matching of the number of incoming
axons to the number of receiving cells
• A neurotropin is a chemical that promotes the survival and activity of
neurons (i.e., NGF).
• Axons that are not exposed to neurotropins after making connections
undergo apoptosis - Preprogrammed mechanism of cell death.
• Therefore, the healthy adult nervous system contains no neurons that
failed to make appropriate connections.
• The elimination of massive cell death is part of normal development
and maturation.
• After maturity, the apoptotic mechanisms become dormant.
• The visual cortex is actually thicker in blind people because due to a
lack of visual stimuli. It cannot prune out ineffective neurons.
The Vulnerable Developing Brain
• Early stages of brain development are critical for normal development
later in life.
• The early stages of brain development are critical. The developing
brain is highly vulnerable to malnutrition, toxic chemicals, and
infections that would produce only mild problems at later ages.
• A mutation on one gene can lead to many defects.
• Chemical distortions in the brain during early development can cause
significant impairment and developmental problems.
Fetal alcohol syndrome is a condition that children are born with if the
mother drinks heavily during pregnancy.
The condition is marked by the following:
• Hyperactivity and impulsiveness
• Difficulty maintaining attention
• Varying degrees of mental retardation
• Motor problems and heart defects
• Facial abnormalities
• The dendrites of children born with fetal alcohol syndrome are short
with few branches.
• Exposure to alcohol in the fetus brain suppresses glutamate and
enhances the release of GABA.
• Many neurons consequently receive less excitation and exposure to
neurotrophins than usual and undergo apoptosis.
• Children of mothers who smoked cigarettes or used cocaine during
pregnancy are at increased risk for ADHD and other behavioral
deficits.
• Children of mothers who used antidepressant drugs during pregnancy
have an increased risk of heart problems.
• Mother’s stress can affect the health of her children
Differentiation of the Cortex
• Neurons in different parts of the brain differ from one another in their
shape and chemical components.
• Immature neurons transplanted to a developing part of the cortex
develop the properties of the new location.
• Neurons transplanted at a later stage of development develop some
new properties but retain some of old properties.
• Example: ferret experiment
Fine-Tuning by Experience
• The brain has some limited ability to reorganize itself in response to
experience.
• Axons and dendrites continue to modify their structure and
connections throughout the lifetime.
• Dendrites continually grow new spines.
• The gain and loss of spines indicates new connections, which relates
to learning.
• Rats raised in an enriched environment develop a thicker cortex and
increased dendritic branching.
• Measurable expansion of neurons has also been shown in humans as a
function of physical activity.
• The thickness of the cerebral cortex declines in old age, but much less in
those that are physically active.
• Once believed that teaching a child a difficult concept (e.g., Greek,
advanced math, etc.) would enhance intelligence in other areas. This
concept is known as “far transfer”.
• Evidence shows that skills associated with the practiced task transfer, but
not other skills. The brain cannot be “exercised” like a muscle
• Neurons also become more finely tuned and responsive to experiences
that have been important in the past.
• This may account for the fact that blind people often have enhanced tactile
senses and increased verbal skills.
• The occipital lobe normally dedicated to processing visual information
adapts to also process tactile and verbal information.
• Experiment.
• Extensive practice of a skill changes the brain in a way that improves the
ability for that skill.
• People who learned to read as adults compared to those who never
learned how to read show more gray matter and greater thickness in part
of the corpus callosum.
• MRI studies reveal following: The temporal lobe of professional
musicians in the right hemisphere is 30% larger than non-musicians.
• Thicker gray matter in the part of the brain responsible for hand
control and vision of professional keyboard players.
• Some professions may require skills that are known to form in brain
areas before birth (e.g., phoneticians)
• Practicing a skill reorganizes the brain to maximize performance of
that skill.
• Certain types of training may also exert a bigger effect if they begins
early in life. Example: musicians who began before age 7 showed
advantages over those who started later in life.
• Focal hand dystonia or “musicians cramp” refers to a condition where
the reorganization of the brain goes too far. The fingers of musicians
who practice extensively become clumsy, fatigue easily, and make
involuntary movements. This condition is a result of extensive
reorganization of the sensory thalamus and cortex so that touch
responses to one finger overlap those of another.
Brain Development and Behavioral
Development
• Adolescents tend to be more impulsive than adults.
• Impulsivity can be a problem when it leads to drinking, risky driving,
etc.
• Antisaccade task: looking away from a powerful attention-getter
• Gradually improves during the teenage years
• Adolescents tend to “discount the future”
• Adolescents are not equally impulsive in all situations.
• Peers, amount of time to make decisions, etc., effect their decisions.
• Adolescents’ prefrontal cortexes are relatively inactive in certain
situations, but this may or may not be the cause of impulsivity.
• Neurons alter synapses more slowly in old age.
• Brain structures begin to lose volume
• Research underestimates older people: People vary in respect to
intellectual decline. Older people have a greater base of knowledge
and experience, and many find ways to compensate for losses.
Plasticity After Brain Damage
• Survivors of brain damage show subtle to significant behavioral
recovery.
• Some of the mechanisms of recovery include those similar to the
mechanisms of brain development such as the new branching of
axons and dendrites.
Brain Damage and Short-Term Recovery
Possible causes of brain damage include:
• Tumors
• Infections
• Exposure to toxic substances
• Degenerative diseases
• Closed head injuries
• Types of strokes include:Ischemia: the most common type of stroke,
resulting from a blood clot or obstruction of an arteryNeurons lose
their oxygen and glucose supply
• Hemorrhage: a less frequent type of stroke resulting from a ruptured
artery
• Neurons are flooded with excess blood, calcium, oxygen, and other
chemicals
• Ischemia and hemorrhage also cause:
• Edema: the accumulation of fluid in the brain resulting in increased
pressure on the brain and increasing the probability of further strokes
• Disruption of the sodium-potassium pump leading to the
accumulation of sodium ions inside neurons
• Edema and excess potassium triggers the release of the excitatory
neurotransmitter glutamate
• The overstimulation of neurons leads to sodium and other ions
entering the neuron in excessive amounts
• Excess positive ions in the neuron block metabolism in the
mitochondria and kill the neuron
• neurotrophins
• drug called tissue plasminogen activator (tPA) breaks up blood clots
and can reduce the effects of an ischemic strokes
• Research has begun to attempt to save neurons from death by:
• Blocking glutamate synapses
• Blocking calcium entry
• One of the most effective laboratory methods used to minimize
damage caused by strokes is to cool the brain
• Mechanisms are uncertain but cooling someone during the first three
days is beneficial
• Cannabanoids have also been shown to potentially minimize cell loss
after a brain stroke
• Benefits are most likely due to cannabinoids anti-inflammatory effects
• Research shows that they are most effective in laboratory animals
when taken before the stroke
• Following brain damage, surviving brain areas increase or reorganize
their activity
• Diaschisis: decreased activity of surviving neurons after damage to
other neurons
• Because activity in one area stimulates other areas, damage to the
brain disrupts patterns of normal stimulation
• Use of drugs (stimulants) to stimulate activity in healthy regions of
the brain after a stroke may be a mechanism of later recovery
• Destroyed cell bodies cannot be replaced, but damaged axons do
grow back under certain circumstancesIf an axon in the peripheral
nervous system is crushed, it follows its myelin sheath back to the
target and grows back toward the periphery at a rate of about 1 mm
per day
• Damaged axons only regenerate one to two millimeters in mature
mammals
• Paralysis caused by spinal cord damage is relatively permanent
• Scar tissue makes a mechanical barrier to axon growth
• Glia cells reacting to damage in CNS release chemicals that inhibit
axon growth
• Research on building protein bridges may help