Download Neural Development

Motor cortex
Somatosensory cortex
Sensory associative
cortex
Pars
opercularis
Visual associative
cortex
Broca’s
area
Visual
cortex
Primary
Auditory cortex
Wernicke’s
area
Neural Development
[Adapted from Neural Basis of Thought and Language
Jerome Feldman, Spring 2007, [email protected]
Lecture Overview
Summary Overview
 Development from embryo
 Initial wiring
 Activity dependent fine tuning
 Additional information/details

 Principles
of Neural Science. Kandel,
Schwartz, Jessell, Mcgraw-Hill (2000).
How does this happen
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Many mechanisms of human brain development remain
unclear, but
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Neuroscientists are beginning to uncover some of these complex
steps through studies of
the roundworm, fruit fly, frog, zebrafish, mouse, rat, chicken, cat
and monkey.
Many initial steps in brain development are similar
across species, while later steps are different.
By studying these similarities and differences, we can
learn how the human brain develops.
Summary Overview
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The Amoeba (ref. book) uses
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complex sensing molecules penetrating its cell membrane to
trigger
chemical mechanisms that cause it to move its blobby body
towards food and away from harmful substances.
Neurons are also cells and,
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in early development, behave somewhat like Amoeba in
approaching and avoiding various chemicals.
But rather than the whole cell moving, neural growth involves the
outreach of the cell’s connecting pathway (axon) towards its
downstream partner neurons.
Summary Overview
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The basic layout of visual and other maps is
established during development by millions of
neurons
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each separately following a pattern of chemical markers to
its pre-destined brain region and specific sub-areas within that
region.
For example, a retinal cell that responds best
to red light
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in the upper left of the visual field will connect to cells in the brain
that are tuned to the same properties and
 these cells, will link to other cells that use these particular properties
giving rise to specific connectivity and cell receptive field properties
(topographic maps).
Summary Overview
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In the course of development,
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detector molecules in the growing neuron interact with
guide molecules to route the connection to the right general
destination, sometimes over long distances as in the
connection from the spinal cord to the knee.
This process will get neural connections to the
right general area, but
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aligning the millions of neurons in visual and other neural
maps also involves
chemical gradients, again utilizing mechanisms that are very
old in evolutionary terms.
Summary Overview
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When an axon tip gets to an appropriately
marked destination cell, the contact starts a
process that develops rudimentary synapses.
Local competition among neural axons with
similar marker profiles produces some further
tuning at the destination.
In fact, the initial wiring is only approximate and
leaves each neuronal axon connected to
several places in the neighborhood neurons.
Summary Overview:
Activity Dependent Tuning
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A second, activity dependent, mechanism is
required to complete the development process.
The initial chemical wiring produces many more
connections and more neurons than are present
in adult brains.
The tuning of neural connections is done by
eliminating the extra links, as well as the
strengthening functional synapses based on
neural activity.
Lecture Overview
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Summary Overview
Development from embryo
 Neural tube development
 Cell division and neuronal identity
 Mechanisms for cell type formation
communication
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Initial wiring
Activity dependent fine tuning
Plasticity and Learning
and
Development from Embryo
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The embryo has three primary layers that
undergo many interactions in order to evolve
into organ, bone, muscle, skin or neural tissue.
 The
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outside layer is the ectoderm
(skin, neural tissue),
the middle layer is the mesoderm
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(skeleton, cardiac) and
 inner
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layer is the endoderm
(digestion, respiratory).
Neural Tissue
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The skin and neural tissue arise from a
single layer, known as the ectoderm
 in
response to signals provided by an adjacent
layer, known as the mesoderm.
 A number of molecules interact to determine
whether the ectoderm becomes neural tissue or
develops in another way to become skin
Neural Tube formation
BRAIN DEVELOPMENT. The human brain and nervous system begin to
develop at three weeks’ gestation as the closing neural tube (left).
By four weeks, major regions of the human brain can be recognized in
primitive form, including the forebrain, midbrain, hindbrain, and optic
vesicle (from which the eye develops).
Irregular ridges, or convolutions, are clearly seen by six months.
Brain Weight
Lecture Overview
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Summary Overview
Development from embryo
 Neural tube development
 Cell division and neuronal
 Cell communication
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identity
Initial wiring
Activity dependent fine tuning
Plasticity and Learning
Development and Infant behavior
Neural cell categories
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After the ectodermal tissue has acquired its
neural fate,
another series of signaling interactions
determine the type of neural cell.
The mature nervous system contains a vast
array of cell types, which can be divided into two
main categories:
 the
neurons, primarily responsible for signaling,
 and supporting cells called glial cells.
Factors/gradients in cell formation
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The destiny of neural tissue depends on a
number of factors, including position, that define
the environmental signals to which the cells are
exposed.
 For
example, a key factor in spinal cord development
is a secreted signaling protein called sonic hedgehog.
 The protein, marks young neural cells that are directly
adjacent to become a specialized class of glial cells.
 Cells further away become the motor neurons that
control muscles.
 An even lower concentration of the signaling protein
promotes the formation of interneurons that relay
messages to other neurons, not muscles.
Timing of Cell Differentiation
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Remarkably, the final position of the neuron (its
laminar position) is correlated exactly to its
birthdate
 The
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birthdate is the time of final mitosis
Cells leaving later migrate past the older
neurons (in deeper cortical layers) to the
outermost cortex.
The layering of the cortex is thus an inside-first
outside-last layering.
As the brain develops, neurons
migrate from the inner surface
to form the outer layers. Left:
Immature neurons use fibers
from cells called glia as
highways to carry them to their
destinations. Right: A single
neuron, shown about 2,500
times its actual size, moves on
a glial fiber. (10-6 m/hr)
Illustration by Lydia Kibiuk,
Copyright © 1995 Lydia
Kibiuk.
Improper migration leads to
diseases including
childhood epilepsy, mental
retardation, lack of sense of
smell and possibly others.
Hiroshima Nagasaki Effects
Lecture Overview
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Summary Overview
Development from embryo
Initial Wiring details
 Axon
Guidance
 Synapse formation
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Activity dependent fine tuning
Plasticity and Learning
Development and Infant behavior
Axon guidance mechanisms
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Axonal growth is led by growth cones
 Filopodia
(growing from axons) are able to sense the
environment ahead for chemical markers and cues.
 Mechanisms are fairly old in evolutionary terms.
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Intermediate chemical markers
 Guideposts
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studied in invertebrates
Short and long range cues
 Short range chemo-attraction and chemo-repulsion
 Long range chemo-attraction and chemo-repulsion
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Gradient effects
Axons locate their target tissues
by using chemical attractants
(blue) and repellants (orange)
located around or on the surface
of guide cells.
Left: An axon begins to grow
toward target tissue. Guide cells
1 and 3 secrete attractants that
cause the axon to grow toward
them, while guide cell 2 secretes
a repellant. Surfaces of guide
cells and target tissues also
display attractant molecules
(blue) and repellant molecules
(orange).
Right: A day later, the axon has
grown around only guide cells 1
and 3.
Synapse formation
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The two cells exchange a variety of signals.
 Vesicles
cluster at the pre-synaptic site
 Transmitter receptors cluster at the post-synaptic site.
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The Synaptic Cleft forms
 When
the growth cone contacts the target cell
(immature muscle cell in the case of a motor neuron),
a cleft (basal lamina) forms.
 Multiple growth cones (axons) get attracted to the
cleft.
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All but one axon is eliminated.
A myelin sheath forms around the synaptic cleft
and the synaptic connection is made.
Overall Process
Basic Process
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Neurons are initially produced along the central canal in the neural
tube.
These neurons then migrate from their birthplace to a final
destination in the brain.
They collect together to form each of the various brain structures
and acquire specific ways of transmitting nerve messages.
Their processes, or axons, grow long distances to find and connect
with appropriate partners, forming elaborate and specific circuits.
Finally, sculpting action eliminates redundant or improper
connections, honing the specificity of the circuits that remain.
The result is the creation of a precisely elaborated child’s network
of 100 billion neurons capable of body movement, perception, an
emotion or a thought.
Nature requires Nurture
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Initial wiring is genetically controlled
 Sperry
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Experiment
But environmental input critical in early
development
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Occular dominance columns
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Hubel and Wiesel experiment
Sperry’s experiment
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Each location in space is seen by a different
location on the retina of the frog
Each different location on the retina is connected
by the optic nerve to a different location in the brain
Each of these different locations in the brain causes
a different movement direction.
In a normal animal, a retinal region which sees in a
particular direction is connected to a tectal region
which causes a movement in that direction
Innervation of the Optic tectum
Nose
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Ganglion Cells in the retina map systematically to cells in
the optic tectum.
The image of the external stimulus is inverted in the
retina and the mapping from the retina to the optic
tectum reverts to the original image.
The Nasal ganglion cells of the retina map to the
posterior region of the Optic tectum and the temporal
ganglion cells map to the anterior region of the tectum
Sperry’s experiment
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Sperry took advantage of the fact that in
amphibians, the optic nerve will regrow after it
has been interrupted
Sperry cut the optic nerve and simultaneously
rotated the eye 180 degrees in the eye socket.
In 'learning’ movements to catch prey, the part of
the retina now looking forward (backward)
should connect to the part of the brain which
causes forward (backward) movement.
Sperry’s findings
After regeneration,
 his animals responded to prey items in
front by turning around and
 to prey items behind by moving forward.
and
 kept doing this even though they never
succeeded in reaching the prey.
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Conclusion from experiment
The conclusion from this (and some
supporting experiments) is
 that the pattern of connections between
retina and tectum, and the movement
information represented is not based on
experience.
 It is defined based on the initial distribution
of chemical markers in the brain.
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Lecture Overview
Summary Overview
 Development from embryo
 Initial wiring
 Activity dependent fine tuning
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The role of the environment
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The development of ocular dominance columns
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Optic nerve fibres from the retina connects to the Lateral
Geniculate Nuclei LGN (in the Thalamus)
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Cat and later monkey (Hubel and Wiesel)
LGN is composed of layers. Each layer receives input (axons)
from a single eye
LGN connects to layer IV of the visual cortex
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The visual cortex develops ocular dominance columns
Cells that are connected to similar layers in the LGN get stacked
together in columns forming stripes.
http://neuro.med.harvard.edu/site/dh/
LGN
VISUAL CORTEX
Monocular deprivation critical
period
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Hubel and Wiesel deprived one of the eyes of
the cat (later macaque monkey) at various times
1 week – 12 weeks (in the monkey case) 4
weeks – 4 months (for the cat).
They found that the ocular dominance cell
formation was most severely degraded if
deprivation occurred at 1 – 9 weeks after birth.
Deprivation after the plastic period had no longterm effect.
Critical Periods in Development
There are critical periods in development
(pre and post-natal) where stimulation is
essential for fine tuning of brain
connections.
 Other examples of columns
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 Orientation
columns
Pre-Natal Tuning: Internally
generated tuning signals
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But in the womb, what provides the feedback to establish
which neural circuits are the right ones to strengthen?
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Not a problem for motor circuits - the feedback and control
networks for basic physical actions can be refined as the infant
moves its limbs and indeed, this is what happens.
But there is no vision in the womb. Recent research shows that
systematic moving patterns of activity are spontaneously
generated pre-natally in the retina. A predictable pattern,
changing over time, provides excellent training data for tuning
the connections between visual maps.
The pre-natal development of the auditory system is also
interesting.
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Infants, immediately after birth, preferentially recognize the
sounds of their native language over others. The assumption is
that similar activity-dependent tuning mechanisms work with
speech signals perceived in the womb.
Post-natal environmental tuning
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The pre-natal tuning of neural connections using simulated
activity can work quite well –
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a newborn colt or calf is essentially functional at birth.
This is necessary because the herd is always on the move.
Many animals, including people, do much of their development after
birth and activity-dependent mechanisms can exploit experience in
the real world.
In fact, such experience is absolutely necessary for normal
development.
Early experiments with kittens showed that there are fairly
short critical periods during which animals deprived of visual
input could lose forever their ability to see motion, vertical
lines, etc.
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For a similar reason, if a human child has one weak eye, the doctor
will sometimes place a patch over the stronger one, forcing the
weaker eye to gain experience.
Adult Plasticity and Regeneration
The brain has an ability to reorganize itself through
new pathways and connections.
• Through Practice:
• London cab drivers, skilled motor regions
• After damage or injury
• Release from inhibition allows neurons to reorganize
• Undamaged neurons make new connections and take
over functionality or establish new functions
• But requires stimulation (phantom limb sensations)
• Stimulation standard technique for stroke victim
rehabilitation
When nerve stimulation changes, as with amputation, the brain reorganizes.
Signals from a finger and thumb of an uninjured person travel independently
to separate regions in the brain's thalamus (left).
After amputation, neurons that formerly responded to signals from the finger
respond to signals from the thumb (right).
Possible explanation for the
recovery mechanism
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The initial pruning of connections leaves some
redundant connections that are inhibited by the
more active neural tissue (lateral inhibition).
When there is damage to an area, the lateral
inhibition is removed and the redundant
connections become active
The neuron then can undergo activity based
tuning based on stimulation.
Summary
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Both genetic factors and activity dependent factors play
a role in developing the brain architecture and circuitry.
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There are critical developmental periods where nurture is
essential, but there is also a great ability for the adult brain to
regenerate.
Questions:
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What computational models satisfy some of the biological
constraints?
What is the relevance of development and learning in language
and thought?