A.1 Neural Development

Understandings: The neural tube of embryonic chordates is formed by in-folding of ectoderm followed by elongation of the tube. Neurons are initially produced by differentiation in the neural tube Immature neurons migrate to a final location An axon grows from each immature neuron in response to chemical stimuli Some axons extend beyond the neural tube to reach other parts of the body A developing neuron forms multiple synapses Synapses that are nut used do not persist Neural pruning involves the loss of unused neurons The plasticity of the nervous system allows it to change Application Incomplete closure of the embryonic neural tube can cause spina bifida Events such as strokes may promote reorganization of brain function Skill Annotation of a diagram of embryonic tissues of Xenopus, used as an animal model, during neurulation

Xenopus – frog embryonic tissue Neural fold Neural plate: folds in, closes  neural tube  elongates into brain/spinal cord Notochord – causes formation of neural plate Ectoderm: brain and nervous system Mesoderm: skeletal, reproductive, circulatory, excretory, muscular Endoderm: lining of gut/organs Archenteron: primitive gut

Neural tube closure: starts from head – proceeds to caudal area Failure to close caudal area by day 27 causes

Field of Study Characteristics needed for model Suitable species Genetics Large numbers and short generation times Fruit fly Baker’s yeast Nematode worm Developmental Biology Robust embryos that are easily manipulated Chicken African clawed frog (Xenopus) Genomic studies, such as genes that cause diseases 60% of human genetic diseases studied have a counterpart in the fruit fly and nematode Nematode Comparative genomics The mouse genome is similarly organized to the human genome Mouse

Neurogenesis - process of differentiation from neuroblasts when specific brain parts form Carry messages Most new neurons in cortex formed between 5th week and 5th month Do not carry messages – 90% brain cells Function – physical and nutritional support of neuron Provide scaffolding for immature neuron migration

During growth – one axon extends Guides direction of growth CAM (cell adhesion molecule) signals growth cone Located on target cell CAM specific receptor Upon reaching target cell: Synaptic connections must be made Via chemical message sent (on surface or excreted extracellular) Neuron synapses with cell Chemotrophic factors Chemoattractive Creates growth and attachment of neuron Chemorepellent

Multiple synapses occur during neurogenesis Single nerve  myriad of synapses to neighboring nerve cells  best fit wins, others die off Strengthening communication in that single connection Controlled by IgCAM (neural adhesion molecule)

Motor neurons extend beyond CNS Gives mammal voluntary control over movement During embryogenesis  neurons follow same pathways to synapse using CAMs Neuromuscular junction

Neural pruning eliminates axons not being used – completed via Microglia cells Remove simple connections – replace with complex ones

Ability to ‘rewire’ differs with age, but always possible Structural plasticity: brain can change its physical structure as a result of learning Example the hippocampus of London taxi drivers is larger than other people’s because of their learnt knowledge Functional plasticity: ability of the brain to move functions from damaged area undamaged area Example: stroke patients learn how to use their arms and legs again.

Stroke patients rewired Axon sprouting Post-stroke neurogenesis Differentiation of glial cells New association with neurons and blood vessels fMRI PET MEG (brain mapping)