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Development
OF THE NERVOUS
SYSTEM
Development and Plasticity
DEVELOPMENT AND CHANGE
IN THE NERVOUS SYSTEM
• The nervous system begins as a hollow tube that later
becomes the brain and spinal cord.
• begins development when the surface of the embryo forms a
groove.
– The edges of this groove curl upward until they meet,
– This makes a groove into a tube.
– About day 18 post-conception
• Development of the nervous system then proceeds in four
distinct stages:
1.
2.
3.
4.
cell proliferation
migration
circuit formation
circuit pruning
proliferation and
migration
• Proliferation:
– Cells that will become neurons divide and multiply at
the rate of 250,000 new cells every minute.
– occurs in the ventricular zone
– Ventricular zone = the area surrounding the hollow tube
that will later become the ventricles and the central
canal.
• Migration: newly formed neurons migrate
– move from the ventricular zone outward to their final
location.
– Aided by specialized radial glial cells.
Circuit formation
• Circuit formation:
– axons of developing neurons grow toward their target cells
– form functional connections.
• Growth cones:
– Form at tip of axons
– Allow axons to find their way form
– These sample the environment for directional cues.
• Chemical and molecular signposts attract or repel the advancing
axon, coaxing it along the way until neuronal axons reach their
final destinations.
– Push, pull, and hem neurons in from the sides
– Chemical & molecular forces guide neuron to intermediate
stations
– Guide past inappropriate targets
circuit pruning
• Pruning: next stage of neural development
– involves elimination of excess neurons and synapses.
– Neurons that unsuccessful in finding a place on a target cell, or
that arrive late, die.
• Second step of circuit pruning: refining organization
– nervous system refines its organization
– continues to correct errors by eliminating large numbers of
excessive synapses.
• Synapses are strengthened or weakened depending on
whether presynaptic and postsynaptic neurons fire
together.
Importance of
neurotrophins
• Neurotrophins = chemicals that enhance
development and survival of neurons
• It is thought that the postsynaptic neuron sends
feedback to the presynaptic terminals in the form
via this chemical
• decreases plasticity (ability to be modified) of these
synapses
Ontogeny recapitulates
Phylogeny!
Anacephaly
•
Anencephaly:
–
–
–
–
•
absence of a major portion of the brain, skull and scalp
These portions of brain fail to develop during embryonic period.
cephalic disorder that results from a neural tube defect
occurs when the rostral (head) end of the neural tube fails to
close, usually between the 23rd and 26th day following
conception
children born with this disorder usually only lack
a telencephalon: the cerebral hemispheres
– remaining structure usually covered only by a thin layer of
membrane
– skin, bone, meninges, etc. are all lacking
•
infants with this disorder usually do not survive longer
than a few hours or possibly days after their birth.
•
In the U.S.: occurs in about 1 out of every 10,000 births.
DEVELOPMENT CHANGEs:
Fetal Alcohol Syndrome
• Fetal alcohol syndrome (FAS)
– often produces mental retardation
– caused by the mother’s use of alcohol during a critical period of brain
development.
• FAS brains are often
– small and malformed
– neurons are dislocated.
• Why? Damage occurs during migration
– many cortical neurons fail to line up in columns as they normally would
– The radial glial cells revert to more typical glial form prematurely.
– Other neurons continue migrating beyond the usual boundary of the
cortex.
A
B.
(a) In the normal brain
the neurons (the dark
spots) tend to line up
vertically.
(
b) In the alcoholexposed brain the
neurons are arranged
randomly. Also, a
number of the neurons
have migrated beyond
the rest of the
neurons.
experience is critical?
• Stimulation continues to shape synaptic
construction and reconstruction throughout the
individual’s life.
• Reorganization
– a shift in connections that changes the function of an area of
the brain.
– Much of the change resulting from experience in the mature
brain involves
Specific areas for specific
functions? Yes and NO!
• Doctrine of specific nerve energies
– Johannes Müller’s
– States: each sensory projection area produces its own unique
experiences regardless of the kind of stimulation it receives.
– Somewhat true
– This is why you “see stars” when your rollerblades shoot out
from under you and the back of your head (where the visual
cortex is located) hits the pavement.
• But functions are also shared and redundant
Fixing the broken brain?
• Why study development of nervous system?
– Gives us clues about how to repair the nervous system when it is
damaged by injury, disease, or developmental error
– Tells about organization, growth, patterns.
• Regeneration:
– Growth of severed axons
– Occurs in amphibians
– Occurs in mammals’ peripheral nervous system.
• Myelin = critical importance:
– provides a guide tube for the sprouting end of a severed neuron to grow
through
– extending axon guided to its destination as it during development
– But: typically only in peripheral nervous system.
neurogenesis
• Neurogenesis:
– the birth of new neurons
– Nervous system could repair itself is if it could grow new
neurons
–
• In adult mammalian brain produces relatively few new
neurons
• BUT: evidence for significant neurogenesis in two
areas.
– hippocampus,
– near the lateral ventricles, supplying the olfactory bulb
– Both important for memory, so perhaps memory does “grow”.
How fix brain if can’t
grow new neurons?
• Compensation
– Having one brain area take over the functions damaged in
another area
– simplest neural recovery: uninjured tissue takes over
functions of lost neurons.
• Presynaptic neurons sprout more terminals
– form additional synapses with their targets and postsynaptic neurons
– Also add more receptor cells.
• Can even get reorganization
– A more dramatic form of neural recovery
– Can involve major brain areas.
Evidence for regeneration?
• Ramón y Cajal declared: no regeneration in the
central nervous system
• Today: data suggest may be several strategies for
inducing self repair following damage.
• How? neuron growth enhancers
– counteracting forces that inhibit regrowth
– providing guide tubes or scaffolding for axons to follow
– Can already repair peripheral nervous system fairly well
How repair CNS?
• The most exciting research uses stem cells to replace
injured neurons.
• Stem cells:
– undifferentiated cells that can develop into specialized cells such as
neurons, muscle, or blood
– Obviously highly controversial.
• One method:
– Placing embryonic stem cells into an adult nervous system
– Encourages new neurons to differentiate into neurons appropriate to that
area.
– But: work like fetal cells- not perfect
• Alternative:?
– Grow your own
– Use stem cells from other body parts