brain development and plasticity · movement to final location ! cell differentiation: taking on...

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BRAIN DEVELOPMENT AND PLASTICITY Dr. Steinmetz 1

OUTLINE

¢ Behavioral Genetics ¢ CNS development ¢ Neuron Migration ¢ Will this neuron survive? ¢ Neuroplasticity and brain damage

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OUTLINE


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REVIEW OF BASIC GENETICS ¢ Genes – units of

DNA ¢ Genotype - a

section of DNA that provides the code for a particular feature (phenotype)

¢ Chromosomes - strands of genes (blueprint)

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WHAT DO GENES DO?

¢ DNA in genes provides code for producing RNA

¢ RNA can be used to create proteins or enzymes � proteins may have a function � enzymes may act as a signal to

turn on / off other biological functions 5

GENES DEFINE PHYSICAL CHARACTERISTICS.

¢ Dominant gene (BB) & Recessive gene (bb) ¢ Homozygous (BB, bb) & Heterozygous (Bb)

BB Eye Color

bb

Bb Bb BB

bb

Possibilities BB

b b

Bb Bb Possibilities B

b

B b

Bb Bb Bb

Bb All Heterozygous

Both Heterozygous & Homozygous

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DIRECT EFFECT OF GENES ¢ Genes can influence the structure of our nervous

system

•  This is an example of genes directly affecting behavior by permitting or eliminating a transduction mechanism.

•  Dad is a nontaster & Mom is a taster, they have one child that is a nontaster, what are Mom and Dad’s genes?

Bitter Taste Ability Dominant trait (T) = Can taste PROP Recessive trait (t) = Can NOT taste PROP

TT

t t Tt

Tt Tt

Tt T t

T t Tt

Tt TT

tt

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OUTLINE


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THE GENESIS AND DEATH OF NEURONS

¢ Cell generation/proliferation: Mitosis

¢ Cell migration: Movement to final location

¢ Cell Differentiation: taking on the appearance and characteristics of a neuron

¢ Apoptosis: programmed cell death 9

DEVELOPMENT OF CNS SHAPE

Neural plate then Neural grove then Neural tube 10

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BRAIN DEVELOPMENT

¢ Astonishing rate of cell division � 250,000 new

neurons per minute

� Billions of neurons

� Trillions of synapses

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UNSCRAMBLE THESE STEPS

¢ Synaptogenesis ¢ Proliferation ¢ Apoptosis ¢ Myelination ¢ Migration ¢ Differentiation

Which two are the most likely to happen throughout life?

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ANSWER

1.  Proliferation 2.  Migration 3.  Differentiation 4.  Myelination 5.  Synaptogenesis 6.  Apoptosis All of these happen throughout

life, but mostly myelination and synaptogenesis.

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PROLIFERATION: THE GENESIS OF NEURONS

¢ Myelination ¢ Synaptogenesis

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EMBRYO IMAGES

¢ http://www.med.unc.edu/embryo_images/unit-welcome/welcome_htms/contents.htm

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OUTLINE


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6 STAGES OF NEURON DEVELOPMENT

1.  Proliferation 2.  Migration 3.  Differentiation 4.  Myelination 5.  Synaptogenesis 6.  Apoptosis

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http://www.youtube.com/watch?v=FZ3401XVYww&feature=related

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HOW ARE APPROPRIATE BRAIN CONNECTIONS MADE?

¢ Is the brain’s structure genetically determined?

¢ How do genes work?

¢ DNA found on chromosomes in nucleus Nucleic acids:

Adenine, Guanine, Cytosine, Thymine

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HOW ARE APPROPRIATE BRAIN CONNECTIONS MADE?

¢ Less than 50,000 different genes in brain

¢ But, trillions of synapses ¢ Can’t be under total genetic

control

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BRAIN REGENERATION/REPAIR STUDIES MAY REVEAL WHAT HAPPENS DURING BRAIN DEVELOPMENT

¢ R. Sperry’s studies in frogs

¢ Cut optic nerve and then inverted eye

¢ Axons grew back to original targets

¢ What was “up” looked “down”

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SPERRY’S EXPERIMENT

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BRAIN REGENERATION/REPAIR STUDIES MAY REVEAL WHAT HAPPENS DURING BRAIN DEVELOPMENT

¢ Craner et al., 1992 – rat study

¢ Fetal retinal transplant in brain projected to appropriate targets

¢ How do they “know” where to go?

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PIONEER NEURONS ¢ Targets are not there when

subcortical neurons are developing

¢ Sub-plate produces cells that migrate to border of cortex

¢ Pioneer cells set pathways for future neurons – then die leaving radial glia as guideposts

¢ But, how do pioneer neurons “know” where to go?

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GROWTH CONE GUIDANCE Filopodia

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GUIDANCE MECHANISMS ¢ Contact attraction; Chemoattraction ¢ Contact repulsion; Chemorepulsion

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DIFFERENTIATION OF NEURONS

¢ Neurotrophins provide a signal for neural differentiation once migration target is reached

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MYELINATION ¢ Oligodendrocytes

– CNS – form multiple sheaths w/ branching arms

¢ Schwann cells – PNS – form singular sheath

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SYNAPTOGENESIS OF NEURONS

¢ Similar to proliferation, during synapse formation there is an over-production of synapses

¢ Synapses continue to form through the first couple of years of life

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OUTLINE


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WILL THIS NEURON SURVIVE?

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NEUROTROPHINS & RECEPTORS

¢ Neurotrophins - chemicals promoting neuron survival & connectivity � Nerve Growth Factor (NGF) � Neurotrophin-3, -4, -5 � Brain-derived Neurotrophic Factor (BDNF)

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NERVE GROWTH FACTOR (NGF)

Rita Levi-Montalcini, 1954, 1956, 1972 36

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1.  Proliferation 2.  Migration 3.  Differentiation 4.  Myelination 5.  Synaptogenesis 6.  Apoptosis 37

APOPTOSIS ¢ Apoptosis - if no

appropriate target by a certain age, the neuron initiates a programmed cell death

¢ Increase of Ca2+ signals release of Diablo protein

¢ Diablo disables the IAP (Inhibitors of Apoptosis Proteins)

¢ 20-80% of neurons die 38

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NEURAL DARWINISM: PROGRAMMED CELL DEATH (APOPTOSIS)

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USE IT OR LOSE IT!

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IMPORTANCE OF NEURAL ACTIVITY

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¢ Axonal remolding (Shatz, 1992)

� neurons grow to many addresses ¢ correct address...remain

¢ incorrect address...eliminated

¢ Neurons that fire together, wire together

IN CLASS ASSIGNMENT

¢ What would happen if someone injected antibodies that block nerve growth factor into a developing nervous system?

¢ What would happen if you injected nerve growth factor into a certain area?

¢ Can you think of a way that this could be useful or harmful? 42

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¢ Nerve growth factor study: ¢ http://www.adcs.org/studies/ngf.aspx

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OUTLINE


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Fig. 5-12, p. 133

Brain correlates of extensive music practice

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RECENT HUMAN DATA: PARALLEL BETWEEN DEVELOPMENT AND BRAIN REPAIR

v Data suggest that the phantom is in the brain and that the brain reorganizes after damage to a limb

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THE CASE OF V.Q.

v  Amputated left arm of 17-year old male

v  Mapped digits on regions of face

v  Water trickled on cheek also felt in phantom limb

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SOMATOSENSORY CORTEX

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PHANTOM LIMBS http://www.youtube.com/watch?v=PpEpj-JgGDI How does the brain re-organize following double hand amputation? http://sciencenow.sciencemag.org/cgi/content/full/2009/406/1

http://www.aolnews.com/2011/02/12/chase-britton-boy-without-a-cerebellum-baffles-doctors/?icid=maing|main5|dl2|sec1_lnk3|43665&a_dgi=aolshare_facebook

How does the brain re-organize following birth defects?

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COLLATERAL SPROUTING

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MARK ROSENZWEIG ENRICHED ENVIRONMENT STIMULATES BRAIN GROWTH

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DEVELOPMENT OF THE BRAIN ¢ Rats in enriched environment =

�  thicker cortex �  increased dendritic branching

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ENHANCED ARBORIZATION OF DENDRITES

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FOR NEXT TIME…

¢ Study for Exam 1 ¢ After that: read Chapter 8 - Movement

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brain development and plasticity · movement to final location ! cell differentiation: taking on...

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