Chapter 9 Development of the Nervous System

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Chapter 9Development of the Nervous System

• From Fertilized Egg to You

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Neurodevelopment

• Neural development an ongoing process, the
  nervous system is plastic
• Complex
• Experience plays a key role
• Dire consequences when something goes wrong

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Case 9-1
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The Case of Genie

• What impact does severe deprivation have on
  development?
• At age 13, Genie weighed 62 pounds and could not
  chew solid food
• Beaten, starved, restrained, kept in a dark room,
  denied normal human interactions
• Can the damage be undone?

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The Case of Genie

• Genies story is often cited for what it told us
  about language development (she only uses short
  utterances), but it also illustrates the impact
  of abuse on all aspects of behavior
• No response to temperature extremes
• Unable to chew
• Extremely inappropriate reactions (silent
  tantrums)
• Easily terrified
• How can neurodevelopment explain this?

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Phases of Development

• Ovum sperm zygote
• Cells then multiply and
• Differentiate
• Move and take their appropriate positions
• Make the needed functional relations with other
  cells
• Developing neurons accomplish these things in 5
  phases

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The 5 Phases

• Induction of the neural plate
• Neural proliferation
• Migration and Aggregation
• Axon growth and synapse formation
• Neuron death and synapse rearrangement

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Induction of the Neural Plate

• A patch of ectodermal tissue on the dorsal
  surface of the embryo
• Development induced by chemical signals from the
  mesoderm (the organizer)
• Visible 3 weeks after conception
• 3 layers of embryonic cells
• Ectoderm outermost, mesoderm middle, endoderm
  - innermost

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Induction of the Neural Plate

• Part of induction is inhibition of bone
  morphogenetic proteins (BMP) that suppress
  neurodevelopment
• Totipotent earliest cells of embryo have the
  ability to become any type of body cell
• With the development of the neural plate cell
  destinies become specified cells are
  multipotent able to develop into any type of
  mature nervous system cell

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Stem cells

• Neural plate cells are often referred to as stem
  cells. Stem cells
• seem to have an unlimited capacity for
  self-renewal
• can develop into different mature cell types
  (totipotent)
• As the neural tube develops specificity
  increases, resulting in glial and neural stem
  cells (multipotent)

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Neural Proliferation

• Neural plate folds to form the neural groove
  which then fuses to form the neural tube
• Inside will be the cerebral ventricles and neural
  tube
• Neural tube cells proliferate in species-specific
  ways 3 swellings at the anterior end in humans
  will become the forebrain, midbrain, and hindbrain

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Figure 9-1
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Migration

• Once cells have been created through cell
  division in the ventricular zone of the neural
  tube they migrate
• Migrating cells are immature, lacking axons and
  dendrites
• Radial migration towards the outer wall of the
  tube
• Tangential migration at a right angle to radial
  migration, parallel to the tube walls
• Most cells engage in both types of migration

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Figure 9-2
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Migration

• Two types of neural tube migration
• Radial migration moving out usually by moving
  along radial glial cells
• Tangential migration moving up
• Two methods of migration
• Somal an extension develops that leads
  migration, cell body follows
• Glial-mediated migration cell moves along a
  radial glial network

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Neural crest

• A structure dorsal to the neural tube and formed
  from neural tube cells
• Develops into the cells of the peripheral nervous
  system
• Cells migrate long distances

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Figure 9-3
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Aggregation

• the process of cells that are done migrating
  aligning themselves with others cells and forming
  structures.
• Cell-adhesion molecules (CAMs) aid both
  migration and aggregation
• CAMs found on cell surfaces, recognize and adhere
  to molecules

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Axon Growth and Synapse Formation

• Once migration is complete and structures have
  formed (aggregation), axons and dendrites begin
  to grow
• Growth cone at the growing tip of each
  extension, extends and retracts filopodia as if
  finding its way
• Chemoaffinity hypothesis postsynaptic targets
  release a chemical that guides axonal growth
  but this does not explain the often circuitous
  routes often observed

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Figure 9-4
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• Growth cones turning at a boundary
• http//www2.umdnj.edu/7egeller/lab/boundmov.htm

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Figure 9-5
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Axon growth - Since Sperry

• Mechanisms underlying axonal growth are the same
  across species
• A series of chemical signals exist along the way
  attracting and repelling
• Such guidance molecules are often released by
  glia
• Adjacent growing axons also provide signals

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Axon growth

• Pioneer growth cones the 1st to travel a route
  follow guidance molecules
• Fasciculation the tendency of developing axons
  to grow along the paths established by preceding
  axons
• Topographic mapping e.g. from retina to the
  optic tectum
• At first mapping assumed to be point to point
• Current evidence suggests mapping more flexible-
  e.g. regeneration studies when optic nerve cut
  and part of retina or optic tectum destroyed
• Topographic gradient hypothesis

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Figure 9-6
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Figure 9-7
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Synaptogenesis

• Formation of new synapses
• Depends on the presence of glial cells
  especially astrocytes
• High levels of cholesterol are needed supplied
  by astrocytes
• Chemical signal exchange between pre and
  postsynaptic neurons is needed
• A variety of signals act on developing neurons

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Neuron Death and Synapse Rearrangement

• 50 more neurons than are needed are produced
  death is normal
• Neurons die due to failure to compete for
  chemicals provided by targets
• Increase targets decreased death
• Destroy some cells increased survival of
  remaining cells
• Increase number of innervating axons decreased
  proportion survive

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Life-preserving chemicals

• Neurotrophins promote growth and survival,
  guide axons, stimulate synaptogenesis
• Nerve growth factor (NGF)
• Both passive cell death (necrosis) and active
  cell death (apoptosis)
• Apoptosis is safer than necrosis cleaner

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Figure 9-8
Synapse Rearrangement
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Postnatal Cerebral Development Human Infants

• Postnatal growth is a consequence of
• Synaptogenesis
• Myelination sensory areas and then motor areas.
  Myelination of prefrontal cortex continues into
  adolescence
• Increased dendritic branches
• Overproduction of synapses may underlie the
  greater plasticity of the young brain

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Development of the Prefrontal Cortex

• Believed to underlie age-related changes in
  cognitive function
• No single theory explains the function of this
  area
• Prefrontal cortex plays a role in working memory,
  planning and carrying out sequences of actions,
  and inhibiting inappropriate responses

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Effects of Experience on Neural Circuits

• Neurons and synapses that are not activated by
  experience usually do not survive use it or
  lose it.
• Humans are uniquely slow in neurodevelopment
  allows for fine-tuning
• How do nature and nurture interact to modify the
  early development, maintenance, and
  reorganization of neural circuits?

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Early Studies of Experience and Neurodevelopment

• Early visual deprivation
• fewer synapses and dendritic spines in 1 visual
  cortex
• deficits in depth and pattern vision
• Enriched environment
• thicker cortices
• greater dendritic development
• more synapses per neuron

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Competitive Nature of Experience and
Neurodevelopment

• Monocular deprivation changes the pattern of
  synaptic input into layer IV of V1
• Altered exposure during a sensitive period leads
  to reorganization
• Active motor neurons take precedence over
  inactive ones

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Figure 9-9
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Effects of Experience on Topographic Sensory
Cortex Maps

• Cross-modal rewiring experiments demonstrate the
  plasticity of sensory cortices with visual
  input, auditory cortex can see
• Change input, change cortical topography -
  shifted auditory map in prism-exposed owls

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Effects of Experience on Topographic Sensory
Cortex Maps

• Neural activity prior to sensory input plays a
  role in development ferret visual development
  disrupted by interference with neuronal activity
  prior to eye opening
• Early music training influences the organization
  of human auditory cortex fMRI studies

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Mechanisms by Which Experience Might Influence
Neurodevelopment

• Many possibilities
• Neural activity regulates the expression of genes
  that direct the synthesis of CAMs
• Neural activity influences the release of
  neurotrophins
• Some neural circuits are spontaneously active and
  this activity is needed for normal development

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Neuroplasticity in Adults

• Mature brain changes and adapts
• Neurogenesis (growth of new neurons) seen in
  olfactory bulbs and hippocampuses of adult
  mammals adult neural stem cells created in the
  ependymal lining in ventricles and adjacent
  tissues

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Figure 9-10
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Effects of Experience on the Reorganization of
the Adult Cortex

• Tinnitus (ringing in the ears) produces major
  reorganization of 1 auditory cortex
• Adult musicians who play instruments fingered by
  hand have an enlarged representation of the hand
  in right somatosensory cortex
• Skill training leads to reorganization of motor
  cortex

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Autism

• 4 of every 10,000 individuals 3 core symptoms
• Reduced ability to interpret emotions and
  intentions
• Reduced capacity for social interaction
• Preoccupation with a single subject or activity
• Intensive behavioral therapy may improve function
• Heterogenous level of brain damage and
  dysfunction varies

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Autism

• Most have some abilities preserved rote memory,
  ability to complete jigsaw puzzles, musical
  ability, artistic ability
• Savants intellectually handicapped individuals
  who display specific cognitive or artistic
  abilities
• 1/10 autistic individuals display savant
  abilities
• Perhaps a consequence of compensatory functional
  improvement in the right hemisphere following
  damage to the left

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Neural Basis of Autism

• Genetic basis
• Siblings of the autistic have a 5 chance of
  being autistic
• 60 concordance rate for monozygotic twins
• Several genes interacting with the environment
• Brain damage tends to be widespread, but is most
  commonly seen in the cerebellum

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Neural Basis for Autism

• Thalidomide given early in pregnancy
  increases chance of autism
• Indicates neurodevelopmental error occurs within
  1st few weeks of pregnancy when motor neurons of
  the cranial nerves are developing
• Consistent with observed deficits in face, mouth,
  and eye control
• Anomalies in ear structure indicate damage occurs
  between 20 and 24 days after conception
• Evidence for a role of a gene on chromosome 7

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Case 9-2
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Figure 9-11
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Figure 9-12
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Williams Syndrome

• 1 of every 20,000 births
• Mental retardation and an uneven pattern of
  abilities and disabilities
• Sociable, empathetic, and talkative exhibit
  language skills, music skills and an enhanced
  ability to recognize faces
• Profound impairments in spatial cognition
• Usually have heart disorders associated with a
  mutation in a gene on chromosome 7 the gene
  (and others) are absent in 95 of those with
  Williams

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Williams Syndrome

• Variety of abilities like autistics
• Evidence for a role of chromosome 7 as in
  autism
• Underdeveloped occipital and parietal cortex,
  normal frontal and temporal
• elfin appearance short, small upturned noses,
  oval ears, broad mouths

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Think About It

• Compare and contrast autism and Williams syndrome
• What do these disorders demonstrated about
  neurodevelopment?
• How are such development disorders studied?

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Figure 9-13