Structural and functional development of the brain

• The order of major events in brain development is;

  • Cell birth (neurogenesis, gliogenesis)
  • Neural migration
  • Axonal/dendritic outgrowth
  • Programmed cell death
  • Synaptic production
  • Myelination
  • Synaptic elimination/pruning
• Neuronal proliferation occurs in embryonic development, at about 2-3 weeks of development
• Neuronal proliferation is the formation of the putative brain and closure of the neural tube
• Neurogenesis and gliogenesis occur in embryonic development, at about 6 weeks of development
• Neurogenesis and gliogenesis refers to the generation and proliferation of neurons and glia
• The bulk of neurogenesis and gliogenesis is done prenatally, but there is some evidence of postnatal continuation
• Neuronal migration occurs during fetal development, at about 12 weeks of development
• The bulk of neuronal migration is done at the end of the second trimester
• Neuronal migration refers to populations of interneurons that migrate postnatally, but most of it is done in utero
• With neuronal migration, cells reach where they have to go and then differentiate
• Neuronal migration is largely completed by 30 weeks of gestational age
• In passive neuronal migration;

  • Cells push each other out
  • The oldest cells are furthest away
  • It's good for short distance migration
  • It's important for formation of thalamus, dentate gyrus and brainstem
• Active neuronal migration;

  • Movement of younger cells past older cells
  • Younger cells in cortex are on the outside of the brain
  • New populations of neurons are born and migrate past old neurons to form another layer
  • Long distance migration
  • Uses radial glial cells
• Radial neuronal migration;

  • 90% of neurons, migrate from ventricular zones radially to cortex
  • Radial movement - moving along glial cells
• Tangenital (parallel) neuronal migration;

  • GABAergic interneurons
  • Inhibitory neurons migrate tangentially to populate cerebral cortex and other forebrain structures
  • Evidence this continues postnatally
• Axonal/dendritic outgrowth occurs in fetal development, at about 18 weeks of development
• In axonal/dendritic outgrowth, axons need to be produced to find targets and complexes of dendritic trees
• Axonal/dendritic growth continues postnatally for about two years
• During axonal/dendritic outgrowth, dendritic trees receive postsynaptic connections of axons from other neurons and become complex
• Axonal/dendritic outgrowth is one of the biggest drivers of brain growth in the last trimester
• How much the brain grows in the last trimester is largely due to dendritic tree development, as part of axonal/dendritic outgrowth
• Growth cone structure (axonal targeting) as part of axonal outgrowth;

  • Highly motile growth cone ends on axons
  • Contains sensorimotor integrative functions required for axon to move through the brain
  • Sense environment and grow and connect
  • Lamellipodia have finger like projections called filopodia that sense the environment
• Programmed cell death occurs in fetal development, at about 20 weeks of development
• Programmed cell death kills of unwanted neurons and nonfunctional circuits
• Apoptosis kills off unwanted cells
• Programmed cell death starts prenatally and continues postnatally
• Programmed cell death is part of the formation of circuits in the brain
• Neurogenesis exceeds the number of neurons required for a mature CNS, so 50-70% of neurons die by apoptosis after migration
• The order of the apoptotic pathway is;

  1. Pre apoptotic cell
  2. Early apoptotic cell
  3. Late apoptotic cell
• In pre apoptotic cells, the nucleus condenses
• In early apoptotic cells, apoptotic blebs are formed
• In late apoptotic cells, microglia remove debris and phagocytic cells clean up debris
• Apoptosis is a tightly regulated physiological process
• Apoptosis is an energy dependent signalling pathway that produces no inflammatory response
• Apoptosis is selective cell death while necrosis is bulk cell death
• Synaptogenesis refers to synapse formation and production
• Synaptogenesis occurs in fetal development, at about 28 weeks of development
• Synaptogenesis starts late prenatally and continues for about two years postnatally
• Synaptogenesis postnatally is done to refine our circuits and allow synapses to signal between cells
• During synaptogenesis, axons (with growth cones) and dendrites form a synapse with other neurons or tissue (e.g. muscle)