Development and Plasticity of the Brain

Maturation of the Vertebrate Brain

• The human CNS begins to form when the embryo is about 2 weeks old
• The dorsal surface thickens, long thin lips rise, curl and merge forming a neural tube that surrounds a
fluid filled cavity
• As the tube sinks under the surface, the forward end enlarges to form the hindbrain, midbrain and
forebrain. The rest becomes the spinal cord
• At birth, the brain usually weighs 350g, by age 1yo it weighs 1000g close to the adult brain weight of
1200-1400 grams

Growth and Development of Neuron

1. Proliferation - refers to the production of new cells
 Early in development, the cells lining the ventricles of the brain divide. Some cells remain as
they are (stem cells), continuing to divide.
 The others become primitive neurons and glia migrating to different locations
2. Migration - after cells have differentiated as neurons or glia, they move.
 Some neurons move radially from the inside of the brain to outside, some move tangentially
along the surface of the brain.
 Chemicals known as immunoglobulins and chemokines guide neuron migration
 A deficit in these chemicals lead to impaired migration, decreased brain size, decreased axon
growth & mental retardation. \
3. Differentiation - a process wherein a neuron grows its axons and dendrites
 The axon grows first as it migrates to its desired location. After the migrating neuron reaches its
destination, dendrites begin to form.
4. Myelination - the process by which glia produces the insulating fatty sheaths that accelarate
transmission of many vertebrate axons
 It is a later and slower stage or neuronal development and continues gradually for decades
5. Synaptogenesis - the final stage is the formation of the synapses
 This process begins before birth and continues throughout life, as neurons form new synapses
and discard old ones

New neurons later in life

Can the adult brain generate new neurons?
• The traditional belief is that vertebrate brains formed all their neurons in embryological development
or early infancy. Neurons could modify their shape, but the brain could not develop new neurons.
• More recent research found that new neurons form in adults, at the olfactory receptors, neurons in the
hippocampus, and in the song-producing areas of some bird species
• New neurons probably do not form at the adult cerebral cortex.
• Researchers documented this by studying radioactive isotope of carbon
• They examined the carbon in the DNA of various cells: skin cells regenerate every year, skeletal
muscle cells every 15 years or so, while neural cells carbon concentration correspond to the year of
their birth
Qwynzyll Benn I. Estelita BSP S 2F
 • Evidently, the human brain forms few or no new neurons in the cerebral cortex after birth

Determinants of Axon Survival

• Initially the sympathetic nervous system forms far more neurons than it needs. When one of its
neurons forms a synapse on to a muscle, that muscle delivers a protein called nerve growth factor
(NGF) that promotes survival and growth of its axon.
• An axon that does not receive NGF degenerates, and its cell body dies
• If its axon does not make contact with an appropriate post synaptic cell by a certain age, the neuron
kills itself through a process called apoptosis
• The brain's system of overproducing neurons then applying apoptosis enables the CNS to match the
number of incoming axons to the number of receiving cells
• Nerve growth factor (NGF) is a neurotrophin, a chemical that promotes the survival and activity of
neurons
• In addition to NGF, the nervous system responds to BDNF (brain-derived neurotrophic factor) and
several other neurotrophins
• For an immature neuron to avoid apoptosis and survive, it needs to receive neurotrophins not only
from its target cells but also from incoming axons.
• When neurons release neurotransmitters, they also release neurotophins
• Loss of cells in particular brain areas can indicate normal development and maturation

The Vulnerable developing Brain

“It is not birth, marriage, or death, but gastrulation, which is truly the most important time of your life” -
(Lewis Wolpert, 1991)
• Gastrulation - is one of the early stages of embryological development
• The early stages of brain development are critical.
• The developing brain is highly vulnerable to malnutrition, toxic chemical and infections that would
produce only mild problems at later ages.
• E.g. impaired thyroid function produces lethargy in adults but mental retardation in infants.
• A fever is just a symptom for adults but impairs neuron proliferation to a fetus
• The infant brain is highly vulnerable to damage by alcohol.
• Children of mothers who drink heavily during pregnancy are born with
• Fetal Alcohol Syndrome - a condition marked by mental retardation, impulsiveness, hyperactivity,
difficulty maintaining attention, motor problems, heart defects and facial abnormalities.
• When children with FAS reach adulthood, they have an increased risk for alcoholism, drug
dependence, depression and other psychiatric disorders.

Qwynzyll Benn I. Estelita BSP S 2F

 • Even in milder cases, prenatal alcohol exposure is associated with impairments in learning, memory
language and attention.
• Prenatal cocaine use = decreased IQ and language skills & impaired hearing
• Children of mothers who smoked during pregnancy are at increased risk for ADHD, aggressive
behavior, impaired memory and intelligence (Huiznuk & Muider, 2005).
• Stress to the mother changes her behavior in ways that change her offspring's behavior: If a mother
rat is exposed to stressful situations, she becomes more fearful, she spends less the usual amount of
time licking and grooming her offspring, the offspring becomes permanently more fearful in a
variety of situations.

Experience and Dendritic Branching

• Because of the unpredictability of life, our brains have evolved the ability to remodel themselves
(within limits) in response to experiences.
• Axons and dendrites continue to modify their structure throughout life.
• About 6% of dendritic spines appear / disappear within a month (Xu, Pan, Young, Gan, 2007)
• The gain or loss of spine means a turnover of synapses, which probably relates to learning.
• As animals grow older, they continue altering the anatomy of their neurons at a slower pace.
• Laboratory animal studies suggest:
• A rat in a more stimulating environment developed a thicker cortex, more dendritic branching and
improved learning.
• Many of its neurons becomes more finely tuned, responding to a narrow range of stimuli.
• An enriched environment enhanced sprouting of axons and dendrites in a wide variety of other
species.
• Activity improves learning and memory, even for rats in isolation.
• The advice to exercise for your brain's sake is particularly important for older people
• On the average, the thickness of the cerebral cortex declines with advancing age, beginning age 30
and accelerating in later years
• Neurons become less active partly because of decreased blood flow.
• Brain volume and activity decline somewhat less in people who remain mentally active (Schooler,
2007) and much less in people who remain physically active (Colcombe, et.al, 2003)

Plasticity after Brain Damage

• Almost all survivors of brain damage show partial behavioral recovery and in some cases, it is
substantial.
• Some of the mechanisms rely on the growth of new branches of axons and dendrites.
• Understanding the process may lead to better therapies for people with brain damage and to insights
into the functioning of a healthy brain.
• Neuroplasticity - an umbrella term describing lasting change to the brain throughout the person's
life
• The possible cause of brain damage includes tumors, infections, exposure to radiation or toxic
substances, and degenerative conditions such as Parkinson's and Alzheimer's disease.
• In young people, the most common cause is closed head injury, a sharp blow to the head resulting
from an accident, assault, or other sudden trauma that does not actually puncture the brain.
• Another cause is blood clots that interrupt blood flow to the brain.

Qwynzyll Benn I. Estelita BSP S 2F

Types of Stroke
• A common cause of brain damage in older people is temporary loss of blood flow to a brain area
during a stroke, also known as cerebrovascular accident.
Ischemia - the more common type of stroke, the result of a blood clot or or other obstruction in an artery.
Hemorrhage - less common type, the result of a ruptured artery.
• Strokes vary in severity from barely noticeable to immediately fatal.
• Both types of strokes can lead to edema (accumulation of fluid) which increases pressure n the brain
and can lead to additional strokes.

Immediate Treatments for Stroke

• A drug called tissue plasminogen activator (tPA) breaks up blood clots and are used to treat
ischemic strokes.
• To get a significant benefit, patients should receive it within 3 hours after the stroke.
• A serious side effect of it is hemorrhage, and researchers are currently working on reducing side
effects.
• Cooling the brain (33-36 C) for the first 3 days is also beneficial to save neurons in the penumbra -
the region surrounding the immediate damage
• In animals, cannabinoids reduce cell loss after a stroke due to its anti-oxidant / anti-inflammatory
properties as well as injection of omega-3 fatty acids.

Recovery after Brain Damage

• Increased Brain Stimulation
• The Regrowth of Axons
• Sprouting
• Denervation Supersensitivity
• Reorganized Sensory Representations and Phantom Limb
• Learned Adjustments in Behavior
• Increased Brain Stimulation
• Diaschisis (from a Greek term meaning “to shock throughout”) refers to the decreased activity of
surviving neurons after damage to nearby neurons
• Eg. a damage to a part of the left frontal cortex will result to activity decreases in the left temporal
cortex and other areas.
• Electrical stimulation of the hypothalamus of a partially conscious man led to substantial
improvements in self feeding and some intelligible speech
• Use of stimulant drugs in rats & cats promote recovery in movement and depth perception
• Phantom Limb - a continuing sensation of an amputated body part
• The sensation can range from a mild tingling to intense pain
• The phantom sensation may fade within days or weeks, but some cases lasts a lifetime
• Amputees who learn to use an artificial limb report that their phantom sensations gradually disappear
• In sum, most recovery of brain functions after brain damage relies on learning to make better use of
spared functions.
• Most brain damage patients are capable of more than they show because they avoid using skills that
have become impaired or difficult

Qwynzyll Benn I. Estelita BSP S 2F