Brain Development

Lecture 7

PSY391S

John Yeomans

How to Make a Brain

• From Zygote to Brain: 1100 billion cells.• Gene/protein signals in each cell must

interact with environment. D = GE.• Mitosis and cell proliferation.• Blastula and Embryonic Stem cells (7 d).• Gastrula to Ectoderm (10-18 d).

Day 7 Postnatal

Knockouts

Brain Growth

• 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

• 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 & Ch1-4 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 CortexWoolseyBarrel Fields for Vibrissae

Developmental Disorders

Lecture 9

PSY391S

John Yeomans

Causes of Disorders

• Retardation: Genes and Environment.

• Huntington’s and Parkinson’s Diseases.

• Alzheimer’s Disease.

• Ethics of Gene Treatments.

Trisomy 21- Fragile XDown’s

Chromosome Disorders

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

• 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 genelong Gln chainsstriatal degeneration.

• >35 copieslate onset. >100early 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 Ch21Presenilins Ch1

Apolipotropin e4 Ch19