A1 - Neural development

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What is embryogenesis

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1

What is embryogenesis

The development of a fully-formed organism from a fertilised egg

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Where are all tissues derived from?

three initial germ layers (ectoderm, mesoderm, endoderm) formed via gastrulation

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What is neurulation

The process by which a neural tube in embryonic chordates is formed

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Neurulation process

  • Cells located in the outer germ layer (ectoderm) differentiate to form a neural plate

  • The neural plate then bends dorsally (towards the back), folding inwards to form a groove with a neural crest on either side

  • The infolded groove closes off and separates from the neural crest to form the neural tube

  • The neural tube will elongate as the embryo develops and form the central nervous system (brain and spinal cord)

  • The cells of the neural crest will differentiate to form the components of the peripheral nervous system

<ul><li><p><span>Cells located in the </span><strong><span>outer germ layer</span></strong><span> (ectoderm) </span><strong><span>differentiate</span></strong><span> to form a </span><strong><span>neural plate</span></strong></p></li><li><p><span>The </span><strong><span>neural plate </span></strong><span>then </span><strong><span>bends</span></strong><span> dorsally (towards the back), folding inwards to form a groove with a neural crest on either side </span></p></li><li><p><span>The </span><strong><span>infolded groove</span></strong><span> </span><strong><span>closes off </span></strong><span>and </span><strong><span>separates</span></strong><span> from the </span><strong><span>neural crest </span></strong><span>to </span><strong><span>form</span></strong><span> the </span><strong><span>neural tube</span></strong></p></li><li><p><span>The</span><strong><span> neural tube</span></strong><span> will </span><strong><span>elongate</span></strong><span> as the </span><strong><span>embryo develops</span></strong><span> and form the </span><strong><span>central nervous system </span></strong><span>(brain and spinal cord)</span></p></li><li><p><span>The </span><strong><span>cells</span></strong><span> of the </span><strong><span>neural crest</span></strong><span> will </span><strong><span>differentiate</span></strong><span> to form the </span><strong><span>components</span></strong><span> of the </span><strong><span>peripheral nervous system</span></strong></p></li></ul>
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Xenopus and their use

genus of frog that possess robust embryos that can tolerate extensive manipulation

  • therefore they can be used as a suitable animal model for investigating the developmental stages of embryogenesis

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Neurulation in a Xenopus Embryo

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which areas does closure of the neural tube occur more slowly and faster in the embryo?

  • Closure of the neural tube occurs more slowly in the caudal (tail) region of the embryo,

  • while the area where the brain forms is well advanced in closure.

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Spina bifida + effects

a birth defect resulting in the incomplete closure of the neural tube (and associated vertebrae)

  • The vertebral processes do not fuse, leaving the spinal cord nerves exposed and prone to damage

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Normal vs spina bifida vertebrae comparison

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Spina bifida occulta

the splits in the vertebrae are so small that the spinal cord does not protrude (less severe/mild)

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Spina bifida cystica

a meningeal cyst forms (meningocele) which may include the spinal elements (myelomeningocele) (less severe/mild)

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Severe spina bifida - what happens

patients may typically suffer some degree of paralysis, as well as bowel and bladder dysfunction

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Believed cause of spina bifida

Spina bifida is believed to be caused by a combination of genetic and environmental factors

  • The average worldwide incidence of the condition is ~1 in 1,000 births, however marked geographic variation occurs

  • Not having enough folate (folic acid)in the diet during pregnancy is believed to play a significant role in causing spina bifida

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What does the neural tube contain

multipotent neuronal stem cells which can differentiate to form the different types of nerve cells:

  • neurons

  • glial cells

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Neurons

are specialised nerve cells that conduct messages:

  • they can be sensory,

  • motor

  • or relay (interneurons)

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Glial cells

provide physical and nutritional support for the neurons

  • roughly 90% of nerve cells in the brain are glial cells

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How are neurons produced?

Via neurogenesis by progenitor neuroblasts

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Do neurons regenerate?

Not usually.

  • Because most neurons survive for the lifetime of the individual and do not reproduce following embryogenesis

  • Certain brain regions may be capable of adult neurogenesis, but most of the nervous system is incapable of regeneration

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Neuron production via neurogenesis

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What must immature neurons do and why?

Immature neurons must migrate in order to adopt precise final positions that allow for the formation of neural circuitries

  • This migration process is critical for the development of brain and spinal architecture

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2 processes via which neural migration may occur?

glial guidance or somal translocation

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glial guidance

Glial cells may provide a scaffolding network along which an immature neuron can be directed to its final location

<p><strong><span>Glial cells </span></strong><span>may provide a </span><strong><span>scaffolding network </span></strong><span>along which an </span><strong><span>immature neuron </span></strong><span>can be </span><strong><span>directed</span></strong><span> to its </span><strong><span>final location</span></strong></p>
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somal translocation

the neuron may form an extension at the cell’s perimeter and then translocate its soma along this length

<p>the <strong>neuron</strong> may form an <strong>extension</strong> at the <strong>cell’s</strong> <strong>perimeter</strong> and then <strong>translocate</strong> its <strong>soma</strong> along this length</p>
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what does an immature neuron consist of

cell body (soma) containing a nucleus and cytoplasm

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when will axons and dendrites grow from an immature neuron

  • Axons and dendrites will grow from each immature neuron in response to chemical signals from surrounding cells

  • Some axons may be quite short (within the CNS) but others may extend to other parts of the body (within the PNS)

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what are filiopida

a growth cones at the tip of axons that contain highly motile growth filaments

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extension of filiopida results

Extension of these filopodia causes the expansion of the internal cytoskeleton within the growth cone

  • this results in growth

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what is the extension of filiopida controlled by - what does this allow the cells to do

chemical stimuli released from surrounding cells

  • These cells may release chemoattractant signals (grow towards) or chemorepellant signals (grow away)

  • Using these molecular guidance signals, axon growth cones may navigate long distances to reach specific targets

<p><strong><span>chemical</span></strong><span> </span><strong><span>stimuli</span></strong><span> released from </span><strong><span>surrounding cells</span></strong></p><ul><li><p><span>These </span><strong><span>cells</span></strong><span> may </span><strong><span>release</span></strong><span> </span><strong><span>chemoattractant</span></strong><span> </span><strong><span>signals</span></strong><span> (grow </span><u><span>towards</span></u><span>) or </span><strong><span>chemorepellant</span></strong><span> signals (grow </span><u><span>away</span></u><span>)</span></p></li><li><p><span>Using these </span><strong><span>molecular guidance signals</span></strong><span>, </span><strong><span>axon&nbsp;growth cones</span></strong><span> may </span><strong><span>navigate</span></strong><span> long distances to </span><strong><span>reach specific targets</span></strong></p></li></ul>
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what is a synapse

a junction at which a neuron transmits a signal to another cell

  • Most synapses transmit chemical signals, although electrical synapses also exist

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what will a developing neuron form… what will this allow

multiple synapses, creating a vast array of permutable communication pathways

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what will a neuron form and with whawt within the central nervous system

Within the CNS, a neuron may form a synapse with another axon, dendrite or cell body (soma)

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what will a neuron form within the peripheral nervous system

Within the PNS, a neuron may form a synapse with a muscle fibre (neuromuscular) or gland (neuroglandular)

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neurosecretion

Some neurons may form a synapse with capillaries and secrete chemicals directly into the bloodstream (neurosecretory)

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What is the role of synapses in the process of learning? how do neurons evolve / strengthen and weaken

  • During embryonic and early post-natal development, neurons form multiple synapses to maximize available connections.

  • As an organism matures, some synapses are used more frequently, strengthening those connections.

  • Conversely, synapses that are not used as often weaken and do not persist.

  • This process of strengthening and weakening certain neural pathways is essential for learning.

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Neural pruning and how it works

Neural pruning involves the loss of unused neurons (by removing excess axons and eliminating their synaptic connections)

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Infant vs adult brains no. of neurons and no. of synaptic connections

  • Infant and adult brains typically have the same total number of neurons (roughly 100 billion neurons in total)

  • However infant brains form vastly more synaptic connections (approximately twice the number found in adult brains)

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purpose of neural pruning

to reinforce complex wiring patterns associated with learned behaviour

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what influences neural pruning

  • Pruning is influenced by environmental factors and is

  • mediated by the release of chemical signals from glial cells

<ul><li><p><span>Pruning is </span><strong><span>influenced</span></strong><span> by</span><strong><span> environmental factors </span></strong><span>and is</span></p></li><li><p><span> </span><strong><span>mediated</span></strong><span> by the</span><strong><span> release of chemical signals</span></strong><span> from </span><strong><span>glial cells</span></strong></p></li></ul>
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Synaptic Formation and Neural Pruning

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40

Neuroplasticity

the capacity for the nervous system to change and rewire its synaptic connections

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what does neuroplasticity enable

  • enables individuals to reinforce certain connections (learning) or avoid damaged regions

  • enables memory retention and learning

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by which 2 mechanisms is neuroplasticity achieved

via two primary mechanisms

  • rerouting

  • sprouting

<p><span>via two primary mechanisms</span></p><ul><li><p><strong><span>rerouting</span></strong></p></li><li><p><strong><span>sprouting</span></strong></p></li></ul>
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Rerouting

creating an alternative neural pathway by deleting damaged neurons and forming a new pathway between active neurons.

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Sprouting

involves the growth of new axon or dendrite fibres to enable new neural connections to be formed

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45

what is a stroke

is the sudden death of brain cells in a localised area due to inadequate blood flow

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what do strokes result in

This results in the improper functioning of the brain, due to the loss of neural connections in the affected area

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two main types of strokes

  • ischemic strokes

  • hemorrhagic strokes

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48

ischemic strokes

Ischemic strokes result from a clot within the blood restricting oxygenation to an associated region of the brain

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Hemorrhagic strokes

result from a ruptured blood vessel causing bleeding within a section of the brain

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50

how may stroke symptoms be temporary and what is this a result of

  • Strokes symptoms may be temporary if the brain is able to reorganise its neural architecture to restore function

  • Following a stroke, healthy areas of the brain may adopt the functionality of damaged regions

  • This capacity for the restoration of normal function is made possible due to the neuroplasticity of the brain

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51

types of strokes diagram

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