NEUROSCIENE Chapter 23: Wiring the
Brain
• Wiring the brain
o The challenge: precise interconnections among 100 billion neurons
o Brain development
▪ Begins as a tube (neural tube)
▪ Involves neurogenesis, pathway formation, synaptogenesis,
modification of connections
o Wiring in brain
▪ Establishment of correct pathways and targets
▪ Fine tuning based on experience
• The genesis of neurons: cell proliferation
o Neural stem cells give rise to neurons and glia
o Symmetrical division
▪ Gives rise to daughter cell that stays in
subventricular zone
▪ Can further divide
o Asymmetrical division
▪ Gives rise to daughter cell that migrates away
from subventricular zone
▪ Cannot further divide
o Cleavage plane during cell division determines fate of
daughter cells
▪ Differences in distribution of proteins dictates
fate of daughter cells
• Notch-1 and numb both present (symmetrical)
• Notch-1 and numb in separate cells (asymmetrical)
• The genesis of neurons: cell migration
o Pyramidal cells and astrocytes migrate
vertically from ventricular zone of
dorsal telencephalon
▪ Migrate along thin radial
glial fibers
o Inhibitory GABAergic interneurons
and oligodendroglia migrate laterally
from ventral telencephalon
• Cell migration
o First cells to migrate take up residence in “subplate”
layer which eventually disappears
o Next cells to divide migrate to the “cortical plate”
▪ The first to arrive become layer VI
▪ Followed V, IV, and so on
, • The genesis of neurons: cell differentiation
o Cells take the appearance and characteristics of a neuron after
reaching its destination
o In developing pyramidal neurons
▪ Semaphorin 3A gives developing pyramidal neurons their
characteristic shape
• Secreted by cells in marginal zone
• Repels growing axons
• Attracts growing apical dendrite
• Differentiation of cortical areas
o Adult cortical sheet is a “patchwork quilt” of interconnecting neurons
▪ And not the simple layers often described
o Cortical “protomap” in the ventricular zone replicated by radial glial
guides
▪ Pasko Rakic
▪ Set of genetic instructions in ventricular zone dictates cortical
organization
o Thalamic input may also contribute to cortical differentiation
▪ Consequence of subplate neurons
• Attracts thalamic inputs to different parts of developing
cortex (so cortex conversely influences thalamic wiring)
• Transcription factor expression and destination of neural precursor cells
o Neural precursor cell expression of certain transcription factors dictates
destination
▪ Emx2 expression associated with caudal cortical destination
• Emx2 mutant: more cells migrate to rostral areas
▪ Pax6 expression associated with rostral cortical destination
• Pax6 mutant: more cells migrate to caudal areas
• Three phases of axonal guidance
o Pathway
o Target
Brain
• Wiring the brain
o The challenge: precise interconnections among 100 billion neurons
o Brain development
▪ Begins as a tube (neural tube)
▪ Involves neurogenesis, pathway formation, synaptogenesis,
modification of connections
o Wiring in brain
▪ Establishment of correct pathways and targets
▪ Fine tuning based on experience
• The genesis of neurons: cell proliferation
o Neural stem cells give rise to neurons and glia
o Symmetrical division
▪ Gives rise to daughter cell that stays in
subventricular zone
▪ Can further divide
o Asymmetrical division
▪ Gives rise to daughter cell that migrates away
from subventricular zone
▪ Cannot further divide
o Cleavage plane during cell division determines fate of
daughter cells
▪ Differences in distribution of proteins dictates
fate of daughter cells
• Notch-1 and numb both present (symmetrical)
• Notch-1 and numb in separate cells (asymmetrical)
• The genesis of neurons: cell migration
o Pyramidal cells and astrocytes migrate
vertically from ventricular zone of
dorsal telencephalon
▪ Migrate along thin radial
glial fibers
o Inhibitory GABAergic interneurons
and oligodendroglia migrate laterally
from ventral telencephalon
• Cell migration
o First cells to migrate take up residence in “subplate”
layer which eventually disappears
o Next cells to divide migrate to the “cortical plate”
▪ The first to arrive become layer VI
▪ Followed V, IV, and so on
, • The genesis of neurons: cell differentiation
o Cells take the appearance and characteristics of a neuron after
reaching its destination
o In developing pyramidal neurons
▪ Semaphorin 3A gives developing pyramidal neurons their
characteristic shape
• Secreted by cells in marginal zone
• Repels growing axons
• Attracts growing apical dendrite
• Differentiation of cortical areas
o Adult cortical sheet is a “patchwork quilt” of interconnecting neurons
▪ And not the simple layers often described
o Cortical “protomap” in the ventricular zone replicated by radial glial
guides
▪ Pasko Rakic
▪ Set of genetic instructions in ventricular zone dictates cortical
organization
o Thalamic input may also contribute to cortical differentiation
▪ Consequence of subplate neurons
• Attracts thalamic inputs to different parts of developing
cortex (so cortex conversely influences thalamic wiring)
• Transcription factor expression and destination of neural precursor cells
o Neural precursor cell expression of certain transcription factors dictates
destination
▪ Emx2 expression associated with caudal cortical destination
• Emx2 mutant: more cells migrate to rostral areas
▪ Pax6 expression associated with rostral cortical destination
• Pax6 mutant: more cells migrate to caudal areas
• Three phases of axonal guidance
o Pathway
o Target
