Brain Development & Neuroplasticity

Neurodevelopment an ongoing process; the nervous system is plastic A complex process Genetics order but experience modifies Dire consequences when something goes wrong

Brain Development During dev: 250,000 neurons per minute At birth..100 billion neurons; 50 trillion to 1 quadrillion synapses Use it or lose it!

Phases of Development Developing neurons accomplish these things in five phases Induction of the neural plate Neural proliferation Migration and aggregation Axon growth and synapse formation Neuron death and synapse rearrangement

Induction of the Neural Plate A patch of tissue on the dorsal surface of the embryo becomes the neural plate Visible three weeks after conception Three layers of embryonic cells Ectoderm (outermost) Mesoderm (middle) Endoderm (innermost)

Neural Tube Defects Neural tube closes about 28 days after fertilization—WOW! Anencephaly-missing or partial dev of cerebral hemispheres Spina bifida Nearly 50-70% can be prevented with folic acid in diet

Induction of the Neural Plate (continued) Neural plate cells are often referred to as embryonic stem cells Have unlimited capacity for self renewal Can become any kind of mature cell Totipotent – earliest cells have the ability to become any type of body cell Multipotent – with development, neural plate cells are limited to becoming one of the range of mature nervous system cells

How the neural plate develops into the neural tube during the third and fourth weeks of human embryological development

Neural Proliferation Neural plate folds to form the neural groove, which then fuses to form the neural tube Inside will be the cerebral ventricles and neural tube Neural tube cells proliferate in species-specific ways: three swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain Proliferation is chemically guided by the organizer areas – the roof plate and the floor plate

Migration Once cells have been created through cell division in the ventricular zone of the neural tube, they migrate Migrating cells are immature, lacking axons and dendrites

Somal translocation and glia-mediated migration http://www.youtube.com/watch?v=ZRF-gKZHINk http://www.youtube.com/watch?v=4TwluFDtvvY&feature=related Somal translocation and glia-mediated migration

Aggregation After migration, cells align themselves with others cells and form structures Cell-adhesion molecules (CAMs) Aid both migration and aggregation CAMs recognize and adhere to molecules

Axon Growth and Synapse Formation Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow Growth cone – at the growing tip of each extension, extends and retracts filopodia as if finding its way http://www.youtube.com/watch?v=n_9YTeEHp1E&NR=1

Axon Growth A series of chemical signals exist along the way – attracting and repelling Such guidance molecules are often released by glia Adjacent growing axons also provide signals

Axon Growth (continued) Pioneer growth cones – the first to travel a route, interact with guidance molecules Fasciculation – the tendency of developing axons to grow along the paths established by preceding axons

Synaptogenesis Formation of new synapses (at birth each neuron has ~2500 synapses; 2-3 years old 15,000) Depends on presence of glial cells – especially astrocytes High levels of cholesterol are needed – supplied by astrocytes Chemical signal exchange between pre- and postsynaptic neurons is needed

Neuron Death and Synapse Rearrangement ~50% more neurons than are needed are produced – death is normal Neurons die due to failure to compete for chemicals provided by targets The more targets, the fewer cell deaths Destroying some cells increases survival rate of remaining cells Increasing number of innervating axons decreases the proportion that survives

Life-Preserving Chemicals Neurotrophins – promote growth and survival, guide axons, stimulate synaptogenesis Nerve growth factor (NGF) Both passive cell death (necrosis) and active cell death (apoptosis) Apoptosis is safer than necrosis – “cleaner” http://www.youtube.com/watch?v=gYWUTBM8tTo&feature=related As we age, old connections are deleted “synaptic prunining”

Neurons must have purpose to survive Weak or ineffective connections “pruned” Plasticityenables process of developing and pruning connections allowing the brain to adapt to itself to the environment

Plasticity brain changes and adapts Brain’s ability to reorganize itself by forming new neural connections Allows neurons to compensate for injury or disease Allows neurons to adjust to new activities / change in environment

Plastiticy cont. Age-dependent factor Occurs under two conditions Young dev brains more plastic Occurs under two conditions Normal development In response to damage or disease

Hemispherectomy Removal of one hemisphere Last effort to control seizures http://www.youtube.com/watch?v=TSu9HGnlMV0

Neuroplastic Responses Change in neurons Increaed no. of neurons (hippocampus) Increased dendritic branching Increased efficiency in NT production Increased in no. of synapses between neurons

Neurogenesis Physical activity and environmental condition affect proliferation and survival of neurons Serotonin believed to play a key role in neurogenesis In lobsters depletion of serotonin reduced neurogenesis in olfactory areas Lab simulation http://www.wellesley.edu/Biology/Concepts/Simulation/labsimulation.html