Transcript Development - University of Toronto

Brain Development
Lecture 7
PSY391S
John Yeomans
How to Make a Brain
• From Zygote to Brain: 1100 billion cells.
• Gene/protein signals in each cell must
interact with environment. D = GE.
• Mitosis and cell proliferation.
• Blastula and Embryonic Stem cells (7 d).
• Gastrula to Ectoderm (10-18 d).
Day 7
Postnatal
Knockouts
Brain Growth
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Neural plate above notocord.
From neural groove to tube (18-24 d).
Brain regions from bumps (25-100 d).
Encephalons: myel-, met-, mes-, di-, tel-.
Telencephalon development, sulci,
connections and myelination (10-36
weeks).
Life Cycle of Neurons
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Cell proliferation near ventricles.
Migration of daughter cells.
Differentiation into glia and neurons.
Process formation and synaptogenesis.
Selection of synapses and neurons.
Axon growth cones, connections, and
myelination by oligodendroglia.
• Apoptosis (cell death).
Proliferation
Migration
Differentiation
Synaptogenesis
Apoptosis
Axon connections
Wiring the Brain
Lecture 8
PSY391S
John Yeomans
Cortical Development
• Neurons migrate along radial glia and
collect in cortex (Rakic).
• Separation of layers by time of arrival.
• Pyramidal cell development within
columns and axon outgrowth.
• Cerebellar neurons form 3 layers, then
granule cells migrate to inner layer
Neural Migrations
Axon Growth
• Growth cones respond to chemicals.
• Attraction and repulsion (e.g. slit and
netrin, and their receptors).
• Myelination of axons by oligodendoglia.
Myelination
Nerve Growth Signals
• Nerve Growth Factor: Sympathetic & Ch14 basal forebrain neurons.
• Neurotrophic Factors: BDNF, FGF, GDNF.
• Each derived from cultured cells
(sympathetic neurons, fibroblasts, glia,
brain, etc.) and act on special receptors.
Nerve Growth Factor Stimulates Sympathetic Neuron Growth
Activity and Growth
• Thalamus--prenatal retinal activity leads to
separate layers in lateral geniculate.
• Neurons that fire together, wire together.
• Visual cortex--postnatal stimulation leads
to binocular vision and V1 cortical
functions.
• Cortex forms connections by experience
from outside world.
Layers in Lateral Geniculate
Shatz
(Bear 2000)
“Neurons that fire together wire together”
Postnatal Brain Growth
Neurogenesis and Apoptosis
• New neurons made in adult dentate gyrus
and olfactory bulb. Learning?
• Rostral and caudal migration paths.
• Neocortex? Unlikely.
• Apoptosis: Killer caspases and Diablo.
Hubel & Wiesel
Rat Somatosensory Cortex
Woolsey
Barrel Fields for Vibrissae
Developmental Disorders
Lecture 9
PSY391S
John Yeomans
Causes of Disorders
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Retardation: Genes and Environment.
Huntington’s and Parkinson’s Diseases.
Alzheimer’s Disease.
Ethics of Gene Treatments.
Chromosome Disorders
Trisomy 21Down’s
Fragile X
Catenins and Brain Growth
• Cri-du-Chat Syndrome (5p-) causes
severe retardation and smaller brain.
• Delta-catenin at Cri-du-Chat locus causes
severe memory loss in mice.
• Beta-catenin expressed in cortical
proliferation zone.
• Added beta-catenin in transgenic mice
leads to bigger brain, but early death.
• Alpha-catenin deletion leads to
hippocampal and cerebellar disorders.
β-Catenin
Environment and Retardation
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Phenylketonuria (PKU) and phenylalanine.
Spina bifida and folic acid.
Cerebral palsy and hypoxia at birth.
Toxins: lead, alcohol, cocaine.
Treatment and enrichment.
Fetal Alcohol Syndrome
Huntington’s Disease
• Autosomal dominant movement disorder.
• Chromosome 4p linkage in families.
• CAG repeats in huntingtin genelong Gln
chainsstriatal degeneration.
• >35 copieslate onset. >100early
onset.
• Simple genetic test--When should it be
used and by whom?
Parkinson’s Disease
• Due to loss of substantia nigra dopamine
neurons.
• Common in people over 80.
• Treated with L-dopa, DA transplants, or DA
receptor agonists.
• 5-10% early-onset familial: several genes
identified (alpha-synuclein, parkin)
• 90% sporadic: pesticides and MPTP.
• Mitochondria and oxidative stress?
Alzheimer’s Disease
• Poor memory (senile dementia) + neural
changes post mortem (plaques and
tangles).
• B-amyloid and tau proteins.
• Early onset due to APP and presenilins.
• Down’s, APP and Ch21.
• Late onset due to environment and to
ApoE eta4 copies.
Amyloid Plaques and
Neurofibrillary Tangles
Genes and Alzheimer’s Disease
Amyloid Precursor Protein Ch21
Presenilins Ch1
Apolipotropin e4 Ch19