Neural Development
CS182/CogSci110/Ling109
Spring 2008
Srini Narayanan
snarayan@icsi.berkeley.edu
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
o
Many mechanisms of human brain development remain
hidden, but
o
o
o
o
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
o
o
learn how the human brain develops and
how brain abnormalities, such as mental retardation and other
brain disorders, can be prevented or treated.
Summary Overview

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

The basic layout of visual and other maps is established
during development by 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, in turn, 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
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.
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Summary Overview:
Activity Dependent Tuning
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In fact, the initial wiring is only approximate and leaves
each neuronal axon connected to several places in the
neighborhood of each of its eventual partner neurons.
A second, activity dependent, mechanism is required to
complete the development process.
The initial chemical wiring actually produces many more
connections and somewhat more neurons than are
present in adult brains.
The detailed tuning of neural connections is done by
eliminating the extra links, as well as the strengthening
functional synapses based on neural activity.
Summary
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Neural development and learning is moving from
a mystery to routine science.
We know enough to shape theories of how our
brains learn skills, including language, and how
we acquire and use knowledge.
Contemporary theories of learning are also
heavily influenced by psychological experiments,
some of which are described next week.
Lecture Overview
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Summary Overview
Development from embryo
 Neural
tube development
 Cell division and neuronal identity
 Mechanisms for cell type formation and
communication
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Initial wiring
Activity dependent fine tuning
Plasticity and Learning
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

(skeleton, cardiac) and
 inner

layer is the endoderm
(digestion, respiratory).
Neural Tissue

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
In humans, during the 3rd week, this mesoderm begins to
segment. The neural plate folds to form a neural groove and folds.
Other structures
including heart,
Skeleton, etc.
The neural groove fuses dorsally to form a tube at the level of the
4th somite and "zips up” cranially and caudally and the neural
crest migrates into the mesoderm (somites differentiate to form vertebrae,
muscles).
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 identity
 Cell communication
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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 to which it gives
rise.
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

Researchers are finding that the destiny of neural tissue
depends on a number of factors, including position, that
define the environmental signals to which the cells are
exposed.
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For example, a key factor in spinal cord development is a
secreted protein called sonic hedgehog that is similar to a
signaling protein found in flies.
The protein, initially secreted from mesodermal tissue lying
beneath the developing spinal cord, marks young neural cells
that are directly adjacent to become a specialized class of glial
cells.
Cells further away are exposed to lower concentrations of sonic
hedgehog protein, and they become the motor neurons that
control muscles.
An even lower concentration promotes the formation of
interneurons that relay messages to other neurons, not muscles.
Timing of Cell Differentiation

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
Neural Development Time Lapse
Video (Nature Neuroscience 2001)
http://www.nature.com/neuro/journal/v4/n2/extref/nn0201-143-S1.mpg
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

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

The two cells exchange a variety of signals.
 Vesicles
cluster at the pre-synaptic site
 Transmitter receptors cluster at the post-synaptic site.

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 adult network of
100 billion neurons capable of a body movement, a 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
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 innate 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

The role of the environment
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The development of ocular dominance columns
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Retinal input connects to the LGN (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).
The 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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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 prenatally in the retina. A predictable pattern, changing over time, provides
excellent training data for tuning the connections between visual maps.
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The pre-natal development of the auditory system is obviously
relevant
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Research indicates that 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 –
a
newborn colt or calf is essentially functional at birth.
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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.
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In fact, such experience is absolutely necessary for
normal development.
 As
we saw, 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.
Adult Plasticity and Regeneration
The brain has an amazing ability to reorganize itself
through new pathways and connections rapidly.
• Through Practice:
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After damage or injury
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London cab drivers, motor regions for the skilled
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
Summary
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Both genetic factors and activity dependent
factors play a role in developing the brain
architecture and circuitry.
 There
are critical developmental periods where
nurture is essential, but there is also a great ability for
the adult brain to regenerate.
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Next lecture: What computational models satisfy
some of the biological constraints.
Question: What is the relevance of development
and learning in language and thought?
5 levels of Neural Theory of
Language
Spatial
Relation
Motor
Control
Metaphor Grammar
Cognition and Language
abstraction
Computation
Structured Connectionism
Neural Net
Triangle Nodes
SHRUTI
Computational Neurobiology
Biology
Neural
Development
Quiz
Midterm
Finals