Brain development by fjwuxn

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									Brain development

  Nature and nurture
                       Outline

• Part 1: Brain development: A macroscopic perspective
• Part 2: The development of the cerebral cortex
• Part 3: Nature and nurture
                    Part I
Brain development: A macroscopic perspective
                    Part I
Brain development: A macroscopic perspective

        See Chronology of Prenatal
              Development
               p. 110-111
3-4 Weeks
3-4 Weeks
Neural Groove
3-4 Weeks
Neural Groove



 Neural Tube
3-4 Weeks
Neural Groove



 Neural Tube


 Neuroepitheliu
      m
3-4 Weeks
Neural Groove



 Neural Tube


 Neuroepitheliu
      m
    Brain

  Spinal Chord
5 to 6 Weeks
          Nervous system begins to function
  Hind-, mid-, and forebrain are now distinguishable
5 to 6 Weeks
5 to 6 Weeks
5 to 6 Weeks
               Forebrain
5 to 6 Weeks
                Forebrain



Telencephalon
5 to 6 Weeks
                  Forebrain



Telencephalon


       Diencephalon
5 to 6 Weeks
               Forebrain
5 to 6 Weeks
               Forebrain

               Midbrain
5 to 6 Weeks
               Forebrain

               Midbrain

               Hindbrain
          •Neurons forming rapidly
             •1000’s per minute




7 Weeks
          Division of the halves of the brain visible




          14 Weeks
7 Weeks
          •Nerve cell generation complete
            •Cortex beginning to wrinkle
                   •Myelinization




                         6 Months
           14 Weeks
7 Weeks
                                9 Months



                     5 Months
          14 Weeks
7 Weeks
 Telencephalon: C-shaped growth
         Cortex: Folding




                                  9 Months



                     5 Months
          14 Weeks
7 Weeks
 Telencephalon: C-shaped growth
         Cortex: Folding




                                  9 Months



                     5 Months
          14 Weeks
7 Weeks
9 Months
9 Months
9 Months




            Medulla

   Hindbrain Pons

            Cerebellum
9 Months




            Medulla

   Hindbrain Pons

            Cerebellum
9 Months




            Medulla

   Hindbrain Pons

            Cerebellum
9 Months




            Medulla

   Hindbrain Pons

            Cerebellum
9 Months   Controls respiration, digestion, circulation,
                      & fine motor control



              Medulla

   Hindbrain Pons

              Cerebellum
9 Months




           Midbrain
9 Months
              Basic auditory and visual processing




           Midbrain
 9 Months



               Thalamus
Diencephalon
               Hypothalamus
 9 Months
                       Sensory relay station
                        Long-term memory
            Intersection of CNS and hormone system


               Thalamus
Diencephalon
               Hippocampus

               Hypothalamus
9 Months




      Telencephalon

   2 Cerebral hemispheres

  Forms a “cap” over inner
      brain structures
9 Months




  Cross-sectional view
9 Months

                           Cerebral
                         Hemispheres




  Cross-sectional view
9 Months

                           Cerebral
                         Hemispheres

                          Thalamus

                         Hypothalamus



  Cross-sectional view   Hippocampus
9 Months                   As the telencephalon
                         develops, it connects both
                            with itself, and with
                             the diencephalon




  Cross-sectional view
9 Months                   As the telencephalon
                         develops, it connects both
                            with itself, and with
                             the diencephalon


                              Corpus Callosum

                               Internal Capsule



  Cross-sectional view
 9 Months



                Hippocampus
Telencephalon
 9 Months              Thin layer of cells covering
                            both hemispheres




Telencephalon Cortex
Cortex                   High-level visual processing



         Visual Cortex
Cortex                     Auditory & visual processing
                              Receptive language


         Visual Cortex

         Temporal Cortex
Cortex                       Sensory integration
                           Visual-motor processing


         Visual Cortex

         Temporal Cortex

         Parietal Cortex
Cortex                     Higher-level cognition
                               Motor control
                           Expressive language

         Visual Cortex

         Temporal Cortex

         Parietal Cortex

          Frontal Cortex
Cortical Development

 Begins prenatally

 Continues into late
   adolescence
II: The development of the cerebral cortex

            A microscopic view
              Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
              Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
              Development of the Cortex

• 2 types of cells:     Dendrite
• Neurons
• Glial cells
              Development of the Cortex

• 2 types of cells:     Dendrite
• Neurons              Cell body
• Glial cells
              Development of the Cortex

• 2 types of cells:     Dendrite
• Neurons              Cell body
• Glial cells
                         Axon
              Development of the Cortex

• 2 types of cells:     Dendrite
• Neurons              Cell body
• Glial cells
                         Axon

                       Synapse
                Development of the Cortex

  • 2 types of cells:     Dendrite
  • Neurons              Cell body
  • Glial cells
                           Axon

                         Synapse


Transmit information through the brain
               Development of the Cortex

 • 2 types of cells:
 • Neurons
 • Glial cells
     Outnumber neurons 10:1
Nourish, repair, & mylenate neurons
      Crucial for development
               Development of the Cortex

 • 2 types of cells:
 • Neurons
 • Glial cells
     Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
      Crucial for development
               Development of the Cortex

 • 2 types of cells:
 • Neurons
 • Glial cells
     Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
      Crucial for development
 Eg. Oligodendroglia
               Development of the Cortex

 • 2 types of cells:
 • Neurons
 • Glial cells
     Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
      Crucial for development
           8 stages of cortical development
1.   Neural proliferation
2.   Neural migration
3.   Neural differentiation
4.   Axonal growth
5.   Dendritic growth
6.   Synaptogenesis
7.   Myelination
8.   Neuronal death
   1. Neural proliferation
• Begins with neural tube closure
   1. Neural proliferation
• Begins with neural tube closure
   1. Neural proliferation
• Begins with neural tube closure
• New cells born in ventricular layer
   1. Neural proliferation
• Begins with neural tube closure
• New cells born in ventricular layer
• 1 mother cell produces ≈ 10,000
  daughter cells
   1. Neural proliferation
• Begins with neural tube closure
• New cells born in ventricular layer
• 1 mother cell produces ≈ 10,000
  daughter cells
• All neurons (100 billion in total) are
  produced pre-natally
   1. Neural proliferation
• Begins with neural tube closure
• New cells born in ventricular layer
• 1 mother cell produces ≈ 10,000
  daughter cells
• All neurons (100 billion in total) are
  produced pre-natally
• Rate of proliferation extremely
  high; thousands/minute
  2: Cellular migration
• Non-dividing cells migrate from
  ventricular layer
  2: Cellular migration
• Non-dividing cells migrate from
  ventricular layer
• Creates a radial inside-out
  pattern of development
  2: Cellular migration
• Non-dividing cells migrate from
  ventricular layer
• Creates a radial inside-out
  pattern of development
• Importance of radial glial cells
  2: Cellular migration
• Non-dividing cells migrate from
  ventricular layer
• Creates a radial inside-out
  pattern of development
• Importance of radial glial cells
3. Cellular differentiation

• Migrating cells structurally
  and functionally immature
3. Cellular differentiation

• Migrating cells structurally
  and functionally immature
• Once new cells reach their
  destination, particular genes
  are turned growth of
  axons, dendrites, and
  synapses
                 4. Axonal growth

• Growth occurs at a growth cone
                 4. Axonal growth

• Growth occurs at a growth cone


                                    Growth cone
                  4. Axonal growth

• Growth occurs at a growth cone
• Axons have specific targets
• Targets often enormous distances away
• Some axons extend a distance that is 40,000 times
  the width of the cell body it is attached to
• Finding targets ?  chemical & electrical gradients,
  multiple branches
                  5. Dendritic growth
• Usually begins after migration
• Slow
• Occurs at a growth cone
• Begins prenatally, but continues postnatally
• Overproduction of branches in development and resultant
  pruning
• Remaining dendrites continue to branch and lengthen
   6. Synaptogenesis

• Takes place as dendrites and
  axons grow
• Involves the linking together of the
  billions of neurons of the brain
   6. Synaptogenesis

• Takes place as dendrites and
  axons grow
• Involves the linking together of the
  billions of neurons of the brain
• 1 neuron makes up to 1000
  synapses with other neurons
• Neurotransmitters and receptors
  also required
           Overproliferation and pruning

• The number of synapses reaches a maximum at about
  2 years of age
• After this, pruning begins
• By 16, only half of the original synapses remain
  7: Myelinization

• The process whereby glial cells wrap themselves
  around axons
  7: Myelinization

• The process whereby glial cells wrap themselves
  around axons
• Increases the speed of neural conduction
  7: Myelinization

• The process whereby glial cells wrap themselves
  around axons
• Increases the speed of conduction
• Begins before birth in primary motor and sensory
  areas
• Continues into adolescence in certain brain regions
  (e.g., frontal lobes)
                   8: Neuronal death

• As many as 50% of neurons created in the first 7
  months of life die
• Structure of the brain is a product of sculpting as
  much as growth
III: Nature and nurture in brain development
              III: Nature versus nurture
• The adult brain consists of approximately 100 billion
  (surviving) neurons that make trillions of synaptic links
• Functionally highly organized, supporting various perceptual,
  cognitive and behavioural processes
• Perhaps the most complex living system we know
                          Question
• Of all the information that is required to assemble a brain,
  how much is stored in the genes?
• Nature view: argues that most of the information is stored
  in the genes
• Nurture view: brain is structurally and functionally
  underspecified by the genes  emerges probabilistically
  over the course of development
                       Nature View
• (1) Not much is left to chance
                        Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified modules
                       Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified modules
• (3) Each module processes a specific kind of information &
  works independently of other modules
                       Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified modules
• (3) Each module processes a specific kind of information &
  works independently of other modules
• (4) In evolution: modules get added to the “collection”
                       Nature View
• (1) Not much is left to chance
• (2)“The grammar genes would be stretches of
      Brain a collection of genetically-specified modules
               DNA that code for proteins…
• (3) Each module processes a specific kind of information &
     that guide, attract, or glue neurons together
  works independently of other modules
                     into networks that…
          evolution: modules get added to the solution
• (4) Inare necessary to compute the “collection”
             to some grammatical problem.”
• (5) In development: genes that code for modules are
  expressed and modules develop according to these
  instructions
              The nature view: Evidence
• Neurogenesis
• Neuroblasts give rise to a limited
  number of daughter cells
• Cells have a genetically mediated
  memory that allows them to
  remember how many times they
  have divided
             The nature view: Evidence
• Genetics and migration
• Mutant or “knock-out” mice
             The nature view: Evidence
• Genetics and migration
• Mutant or “knock-out” mice
• Cannot produce a class of
  proteins called cell adhesion
  molecules (CAM’s)
• Migration is disrupted because
  cells cannot attach to and
  migrate along glia
             The nature view: Evidence
• Growth of dendrites and axons
• Undeveloped neuron needs to
  establish basic “polarity:”
  which end is which?
             The nature view: Evidence
• Growth of dendrites and axons
• Undeveloped neuron needs to
  establish basic “polarity:”
  which end is which?
• Involves specific proteins
             The nature view: Evidence
• Growth of dendrites and axons
• Undeveloped neuron needs to
  establish basic “polarity:”
  which end is which?
• Involves specific proteins
              The nature view: Evidence
• Growth of dendrites and axons
• Undeveloped neuron needs to
  establish basic “polarity:”
  which end is which?
• Involves specific proteins
• Axons: Affords a sensitivity to
  chemical signals emitted by
  targets
              The nature view: Evidence
• Growth of dendrites and axons
• Undeveloped neuron needs to
  establish basic “polarity:”
  which end is which?
• Involves specific proteins
• Axons: Affords a sensitivity to
  chemical signals emitted by
  targets
            The nature view: Evidence
• Formation of synapses
• Knock-out mice
              The nature view: Evidence
• Formation of synapses
• Knock-out mice
• Staggerer
• Neurons in the cerebellum make contact, but receptor
  surface does not develop
• Thus, a single gene deletion can interfere with the formation
  of synapses in the cerebellum
             The nature view: Evidence
• Cell death
• Cells seem to possess death genes
• When expressed, enzymes are produced that effectively cut-
  up the DNA, and kill the cell
• Similar mechanism may control the timing of neuronal death
                      Nurture view
• (1) Brain organization is emergent and probabilistic not pre-
  determined
• (2) Genes provide only a broad outline of the ultimate
  structural and functional organization of the brain
• (3) Organization emerges in development through over-
  production of structure and competition for survival
•Gerald Edelman: Neural Darwinism
                        Nurture view
•Overproliferation of structures + sensory experience
produce Darwinian-like selection pressures in
development
 • (1) Brain organization is emergent and probabilistic not pre-
•Structures that prove useful in development win the
   determinedfor survival
competition
 • (2) Genes provide off
•The rest are castonly a broad outline of the ultimate
   structural and functional organization of the brain
 • (3) Organization emerges in development through over-
   production of structure and competition for survival
    The “nurture” view:
          Evidence
• Does experience affect developing structures and functions?
• Is the pruning of brain structures systematic?
• Do developing brain regions competitively interact?
The “nurture” view: Evidence             Hubel & Weisel
• Raised kittens but deprived them of visual stimulation to
  both eyes (binocular deprivation)
• No abnormality in the retina or thalamus
The “nurture” view: Evidence            Hubel & Weisel
• Raised kittens but deprived them of visual stimulation to
  both eyes (binocular deprivation)
• No abnormality in the retina or thalamus
• Gross abnormality in visual cortex
• Disrupted protein production caused fewer and shorter
  dendrite to develop, as well as 70% fewer synapses
• Effects only occur early in development, but persist into
  adulthood
• Example: Surgery on congenital cataracts in adult humans
The “nurture” view: Evidence              Hubel & Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
The “nurture” view: Evidence              Hubel & Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• One effect: Monocular deprivation disrupted the
  establishment of ocular dominance columns
   The “nurture” view:   Development of
                           mammalian
         Evidence         visual system
     Adult structure



  Cortex


 Thalamus


Eyes/Retinas
   The “nurture” view:   Development of
                           mammalian
         Evidence         visual system
     Adult structure



  Cortex


 Thalamus


Eyes/Retinas
The “nurture” view: Evidence              Hubel & Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• Sensory input competes for available cortex
• With input from one eye eliminated, no competition
• Therefore, input from uncovered eye assumes control of
  available visual cortex and disrupts the establishment of
  ocular dominance columns
The “nurture” view: Evidence              Hubel & Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• Sensory input competes for available cortex
• With input from one eye eliminated, no competition
          Findings point to the importance of
• Therefore, input from uncovered eye assumes control of
           stimulation from the environment
  available visual cortex and disrupts the establishment of
  ocular dominance columns
The “nurture” view: Evidence Kratz, Spear, & Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired




                                          Hubel & Weise
The “nurture” view: Evidence Kratz, Spear, & Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• A second effect: Residual function of the deprived eye
  competitively inhibited by strong eye
                                          Kratz, Spear, &
The “nurture” view: Evidence
                                              Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• A second effect: Residual function of the deprived eye
  competitively inhibited by strong eye
• Deprived one of experience and then removed strong eye
                                          Kratz, Spear, &
The “nurture” view: Evidence
                                              Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• A second effect: Residual function of the deprived eye
  competitively inhibited by strong eye
• Deprived one of experience and then removed strong eye
• Prior to surgery, stimulation of deprived eye elicited activity
  in only 6% of cortical neurons
                                          Kratz, Spear, &
The “nurture” view: Evidence
                                              Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• A second effect: Residual function of the deprived eye
  competitively inhibited by strong eye
• Deprived one of experience and then removed strong eye
• Prior to surgery, stimulation of deprived eye elicited activity
  in only 6% of cortical neurons: After surgery 31%
                                          Kratz, Spear, &
The “nurture” view: Evidence
                                              Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is severely
  impaired
• A second effect: Residual function of the deprived eye
  competitively inhibited by normal eye
           Findings point to the importance of
             competitive interaction between
• Deprived one of experience and then removed normal eye
                  developing brain regions
• Prior to surgery, stimulation of deprived eye elicited activity
  in only 6% of cortical neurons: After surgery 31%
                                          Impoverished
The “nurture” view: Evidence
                                          Environments
• Animal raised in impoverished environments have brains that
  are 10 to 20% smaller than animal raised in normal
  environments. Why?
                                          Impoverished
The “nurture” view: Evidence
                                          Environments
• Animal raised in impoverished environments have brains that
  are 10 to 20% smaller than animal raised in normal
  environments. Why?
• Decreased glial cell density
• Fewer dendritic spines
• Fewer synapses
• Smaller synapses
The “nurture” view: Evidence                  Sur
• Cortical surgery
• Severed connection between optic nerve and the occipital
  cortex as well as the connection between auditory nerve and
  auditory cortex
• Reconnected optic nerve to auditory cortex
• Animals developed functionally adequate vision
The “nurture” view: Evidence
• Daphnia: A crustacean; easily cloned
• Simple nervous system consisting of several hundred
  neurons
• Connection patterns can be studied directly
• Genetically identical individuals show different patterns of
  neuronal connectivity
               Nurture view: Summary
• Order in the brain is not completely specified by the genes
• Instead, structures and functions emerge probabilistically in
  development through the combined influence of initial over-
  production of structure, neural competition, and experience
                       Conclusions
• Genes are a critical source of guidance for brain development
• Nevertheless, there is abundant shaping and fine-tuning of
  brain structure and function with sensory-experience
      4: Studying human brain development
• Structural and functional change
• How are these changes investigated & what is known?
     4: Studying human brain development
Structural change: Methods




                      Magnetic resonance imaging
     4: Studying human brain development
Structural change: Methods



                             • T1-weighted image
                             • Segmentation
                             • Measure thickness
                             or volume in various
                             regions
        4: Studying human brain development
 Structural change: What do we know?


                            • Total volume increases
                            • White matter increases



Girls Boys


              Giedd et al, Nature Neuroscience, 1999
        4: Studying human brain development
 Structural change: What do we know?


                           • Total volume increases
                           • White matter increases
                           • Grey matter increases
                           and decreases
                           • Heterochronic change



Girls Boys    Giedd et al, Nature Neuroscience, 1999
     4: Studying human brain development
Structural change: What do we know?


                             • Total volume increases
                             • White matter increases
                             • Grey matter increases
                             and decreases
                             • Heterochronic change

    Growth   Shrinkage


                     Sowell, J Neuroscience, 2005
    4: Studying human brain development
Functional change: Methods – ERP’s


                  • Evoked response potentials
                  • Scalp-measured voltages
                  • Many trials averaged
                  • Waveforms
    4: Studying human brain development
Functional change: Methods – ERP’s


 • Advantages
    • Use with infants
    • Inexpensive
    • Relatively non-invasive
    • Excellent temporal resolution
 • Disadvantages
    • Poor spatial resolution
     4: Studying human brain development
Functional change: What do we know?


                 • N170 greater for inverted faces
                 • Faces special
                 • Development?
                 • 12-month-olds show N170 effect
                 • 6-month-olds do not



           de Haan et al, J Cog Neuroscience, 2002
     4: Studying human brain development
Functional change: What do we know?


                  • N170 greater for inverted faces
                  • Faces special
    ERP’s can reveal important changes in brain
                  • Development?
            functioning in infancy and
                  • 12-month-olds
                 early childhood. show N170 effect
                  • 6-month-olds do not



           de Haan et al, J Cog Neuroscience, 2002
    4: Studying human brain development
Functional change: Methods -- fMRI



                         • T2*-weighted image
                         • Blood-oxygenation
                         dependent response
                         (BOLD)
    4: Studying human brain development
Functional change: Methods -- fMRI



                         • T2*-weighted image
                         • Blood-oxygenation
                         dependent response
                         (BOLD)
                         • Eg. Block design

        Time
    4: Studying human brain development
Functional change: Methods -- fMRI


• Advantages
   • Excellent spatial resolution
• Disadvantages
   • Expensive
   • Motion sensitive
   • Limited viability with very young children
       4: Studying human brain development
Functional change: What do we know?

                shape
                                        12-year-olds & adults
                color




       Switch           Repeat            Switch          Repeat
 18s    36s     18s       36s     18s        36s    18s         36s   18s

                                Time



                                                     Morton & Ansari, 2007
     4: Studying human brain development
Functional change: What do we know?


                             All participants

                            Switch > Repeat

                            • Frontal cortex
                            • Parietal cortex


                                   Morton & Ansari, 2007
     4: Studying human brain development
Functional change: What do we know?

                         0.5              Switch    Repeat
                        0.45
                         0.4
                        0.35
                         0.3
                        0.25

           Age x Trial Type interaction reveals
                         0.2
                        0.15

                 development changes
                         0.1
                        0.05
                          0
                               Children            Adults



  R Parietal cortex
     Switch > Repeat
       Only adults
                                             Morton & Ansari, 2007
     4: Studying human brain development
Functional change: What do we know?


 • Challenges
 • What does an Age x TrialType interaction reveal?
      4: Studying human brain development
Functional change: What do we know?


 • Challenges
 • What does an Age x TrialType interaction reveal?
 • Need to consider behavioral performance
 • If perform similarly, could suggest developmental
 change
 • If perform differently, possible that differences in
 brain activity reflect difference in performance not
 age
          Brain Development Conclusions
• (1) Brain changes throughout development both structurally
  and functionally
• (2) Developmental changes occur through and interaction of
  genes and experience.

								
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