Development and Plasticity of The Nervous System

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Development and Plasticity of The Nervous System

• Dr Claire L Gibson (cg95_at_le.ac.uk)
• School of Psychology

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Overview

• Stages of nervous system development
• Cellular interactions
• Role of experience
• Abnormal development

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Background
HOW?

• Behaviour is dependent upon the formation of
  specific interconnections between classes of
  nerve cells with specialised functions

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Gross Development Neuralation
Forebrain
Midbrain
Hindbrain
Spinal cord
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The Neural Tube

• 3 wks after conception
• Failure of the neural tube to close
• 1500 live births
• Folic acid (folate)
• Middle anterior posterior
• Anencephaly
• Spina bifida

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Genes and Environment

• 100,000 genes
• 100,000,000,000,000 neural interconnections
• Epigenetic factors
• Timing
• Genes environment _______
• fully functioning nervous system

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Stages of neuronal development

• Cell birth
• Cell migration
• Cell differentiation
• Cell maturation
• Formation of synaptic contacts
• Cell death/synaptic pruning
• Myelination

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Neural Stem Cells
Cell type
Stem
Precursor
Neural
Glial
Blast
Projecting neuron
Interneuron
Oligodendroglia
Astrocyte
Specialised
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Stage 1 Cell birth

• Neurogenesis birth of neurones
• At the peak of brain development
• 250,00 neurones born per minute
• Majority finished by 5th month of pregnancy
• But, can be switched on by injury?
• Formation of fully functioning nervous system is
  dependent upon connections

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Stage 2 Migration

• Cells need to migrate to an appropriate location
• Migration of neural stem cells away from
  ventricular zone
• Migration begins shortly after neurogenesis
• Radial glial cells
• Chemical signals

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Stage 2 Migration
Inside out development of the cortex
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Stage 3 Differentiation

• Neuroblast specific type of
  neurone
• Genetic signal
• - transcription factors

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Stage 4 Maturation

• Differentiation
• Intrinsic factors
• Immediate environment
• Outgrowth of axons and dendrites (and formation
  of synapses)
• Dendrites dendritic arborisation and growth of
  dendritic spines
• Axons

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Stage 4 Maturation (ii. Axonal Guidance)

• Growth cones respond to
• Cell adhesion molecules
• attractive or repellant
• Tropic molecules
• Chemotropic gradient

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Chemotropic Guidance
Filapodia
Axon terminal
Gradient
Target cell
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Stage 5 Formation of synaptic contacts

• Synaptogenesis occurs when growth cone contacts
  dendrite
• Two-way interaction between axon and dendrite
• Estimated to be 1014 synapses in human cortex

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Stage 6 Cell death

• Normal
• 20 80 cells die
• Apoptosis programmed cell death (PCD)
• Connection with target dependency
• Neurotrophic factors
• e.g. BDNF (brain-derived neurotrophic factor),
• NGF (nerve growth factor)
• Apoptosis

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Stage 6 Synaptic pruning

• Apoptosis accounts for death of excess neurones
  but does not account for pruning of synapses from
  cells that survive
• Synaptic capacity of dendrites varies through
  development
• Synaptic pruning elimination of inappropriate
  and strengthening of appropriate synaptic
  contacts
• How does NS distinguish between appropriate and
  inappropriate?

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Synaptic pruning
Donald Hebb (1949) Neurones that fire together
wire together
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Stage 7 Myelination

• Oligodendroglia myelinating cells of the CNS
• Born shortly after neurones (along with glia)

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Plasticity

• The ability of the nervous system to change with
  experience
• Developmental phenomenon?
• External and internal events

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Experience

• Experience effects our behaviour
• e.g. rats housed in a complex environment vs.
  simple environment
• BUT, does it alter our brain structure?

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Synaptic plasticity

• Long-term potentiation (LTP)
• Long-lasting strengthening of synapses
• High frequency stimulation of incoming pathway
  enhances post-synaptic response to subsequent
  pathway stimulation
• Increased numbers of glutamate receptors
• Long-term depression (LTD)
• Long-lasting weakening of synapses
• Low frequency stimulation
• Decreased numbers of glutamate receptors

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Critical Periods
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Developmental Disorders
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Fetal Alcohol Syndrome

• Vulnerability of developing brain
• Fetal alcohol syndrome
• Decreased altertness, hyperactivity, mental
  retardation, motor problems, heart defects,
  facial abnormalities
• Risk depends on amount AND stage of pregnancy

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Cerebral Palsy
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Summary

• How do we get it right?
• retain capacity for plasticity
• learning and memory
• recovery from injury?

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Focus Points

• What are the stages of neural development?
• What factors influence the formation of neural
  circuits?
• How sensitive is the developing brain to injury?

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Remember

• Basic principles of nervous system development
  any good neuroscience textbook
• Also, see further reading on website
• Thank you !