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Development of the Nervous System. Neurodevelopment. The Case of Genie At age 13, Genie weighed 62 pounds and could not stand erect, chew solid food or control her bladder. She had been starved, beaten , restrained , kept in a dark room, and denied normal human interactions.
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Neurodevelopment The Case of Genie • At age 13, Genie weighed 62 pounds and could not stand erect, chew solid food or control her bladder. • She had been starved, beaten, restrained, kept in a dark room, and denied normal human interactions. • Even with special care and training after rescue, her behavior never became normal(e.g. speaks short, poorly pronounced phrases) Neural development is an ongoing process; the nervous system is plastic. A complex process involving interactions between genes and environment There are dire consequences when something goes wrong.
Phases of Development Ovum + Sperm = Zygote Cell division (multiplication) Differentiation, Migration, and Functional Connections: • Induction of the neural plate • Neural proliferation • Migration and aggregation • Axon growth and synapse formation • Neuron death and synapse rearrangement www.brainfacts.org
Early Development 1 • Ovum + Sperm = Zygote • Cell division • Potency: the ability to develop into different cell types • Fertilized egg: totipotent • Blastocyst: pluripotent (embryonic stem cells) • multipotent; unipotent • “Baby in a Compact Disc”
Neural Plate and Tube Neural plate: a patch of tissue on the dorsal surface of the embryo Induced by chemical signals from the mesoderm (the “organizer”). • Embryonic stage • Neural tube: CNS • Inside tube: ventricles and spinal canal • Neural crest: PNS • Somite: skull and vertebrae thebrain.mcgill.ca
Neural Proliferation 2 Proliferation causes the neural tube to swell Swellings at the anterior end will become the forebrain, midbrain, and hindbrain; 3 become 5
Neural Migration As cells are generated, they begin moving to their “addresses” Time and location govern migration; numerous chemicals attract and repel cells Migrating cells are immature, lacking axons and dendrites Radial and Tangential
Methods of Migration Radial glial cells: initially, scaffold; later, differentiate into neurons, astrocytes, and oligodendrocytes
Aggregation After migration, cells align themselves with others cells and form structures. Aids to migration and aggregation: • Cell-Adhesion Molecules (CAMs) • Gap junctions pass cytoplasm between cells Biological Science 2005
Axon and Dendrite Growth Once neurons have migrated and formed structures, axons and dendrites begin to grow. Growth cone: at the growing tip of each extension; extends and retracts filopodia as if finding its way Remarkably, most growth cones reach their correct targets. Retina Optic tectum
Chemoattraction Netrins + + + + + + + + + + + + + + + + + + + + + + Growth cone + + + + + - - - - - - - - - - - - Contact attraction - - - - - - - - - - - - Ig CAMS Cadherins ECM (e.g., laminins) Neurite Growth: Chemotaxis Hypothesis Chemorepulsion Long-range cues Semaphorins (secreted) Netrins point-to-point or gradient - - - - - - - - - - Contact repulsion Eph Ligands Semaphorins (transmembrane) ECM (for example, tenascins) Short-range cues Guidance molecules released by glia and other growing axons. Fasciculation: the tendency of developing axons to grow along the paths established by preceding axons (i.e, the pioneer growth cone)
Synapse Formation Formation of new synapses is a multi-step process including chemical signal exchange between pre- and post-synaptic neurons Process is enhanced by presence of glial cells —especially astrocytes cholesterol physiology.org
Neuron Death Approximately 50% more neurons than are needed are produced; death is normal. Necrosis vs Apoptosis Apoptosis is triggered if a neuron fails to obtain life-preserving chemicals (e.g., neurotrophins) supplied by its targets. nerve growth factor (NGF)
Synapse Rearrangement A diffuse pattern of synaptic contact is characteristic of early development. A more focused pattern is present after synaptic rearrangement. Two mechanisms: • Apoptosis • “Neurons that fire together, wire together”
Postnatal Cerebral Development Brain volume quadruples between birth and adulthood Growth is a consequence of: • Synaptogenesis • Myelination • Dendritic branching Many opportunities for experience to influence development • Deprivation vs enrichment • Critical period • Sensitive period
Neuroplasticity in Adults The mature brain continues to change and adapt Neurogenesis (growth of new neurons) is seen in the olfactory bulb and hippocampus Experience can reorganize the adult cortex
Disorders of Neurodevelopment Autism • Cognitive impairment • Reduced ability to interpret emotions and intentions • Reduced social interaction • Preoccupation with an activity • Savants Spectrum disorder Incidence: 6.6 per 1,000 Births Planning functions Involved in motor skills and shifting attention Williams Syndrome • Cognitive impairment • Poor spatial abilities, cannot draw • Sociable, empathetic and talkative Incidence: 1 per 7,500 Births Reduced volume Increased volume