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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 & 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 • • • • 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 • • • • • 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 Ch21 Presenilins Ch1 Apolipotropin e4 Ch19