Evolution of the neocortex: a perspective from developmental biology Flashcards
When did humans split from a) mice and 2) macaques?
90-100 million years ago and 25 million years ago
Explain the “evo-devo” approach.
Evo-devo is the realization that developmental neurobiology can explain how genetic info contained within neural progenitor cells regulates the number, type, migration, and allocation of neurons in the developing brain, where they form species-specific circuits. It is an approach we can use to speculate on neocortical evolution, as the remains of our predecessors do not have brains that we can study.
Evo-devo should be distinguished from Haeckle’s law of ontogenetic recapitulation of phylogeny (nineteenth century). Evo-devo approach embraces concept of modularity or functional cellular units, such as segments, somites, limb buds, and cortical columns. Changes in these modules, if not lethal, may be selected if they enhance species survival.
Example: experimental inhibition or over expression of specific genes in cerebral cortex allows us to test their effect on development of cerebral cortex and to draw conclusions on their involvement in increasing evolutionary complexity.
Does the PFC have a counterpart in mouse?
No. It does in macaque, though.
T/F: Mouse, macaque, and human are of a continuous lineage.
FALSE. Mouse and human diverged 90 million years ago, while macaque and human diverged 25 million years ago.
What are some peculiarities of the cerebral cortex?
1) cortex is a cellular sheet composed of pyramidal and interneurons deployed in horizontal layers, intersected by vertical/radial columns that are stereotypically interconnected in the vertical dimension and share extrinsic connectivity.
2) In all mammalian species, none of the cortical neurons are generated within the cortex itself. they are all derived from transient embryonic zones like VZ/SVZ and migrate across IZ to location in the increasingly distant cortical plate.
3) Postmitotic neurons migrate past each sequentially generated generation.
Does enlargement of human neocortex occur mainly by surface area expansion or increase in cortical thickness?
Surface expansion. Thickness of human cortex is only about two times that of mouse.
What is ‘neuropile’?
The tissue situated between neuronal cell bodies, composed of a complex network of neuronal and goal processes including dendrites, dendritic spines, axonal terminals
Name a hypothesis that explains the cellular mechanism underlying the enormous surface expansion of the cortex without a comparable increase in its thickness.
Radial unit hypothesis: an increase in the number of neural stem cells by symmetrical divisions before the onset of neurogenesis would result in an exponential increase in the number of founder cells that give rise to radial cortical columns. At later stages, the number of neurons increases linearly within each column, mostly by asymmetrical divisions of neural progenitors.
How many extra rounds of cellular division in the VZ at the early embryonic stages can account for the 1,000-fold difference in total cortical surface area between mice and humans?
7!
How has the radial unit model been tested? Also, what happens when NSCs express a stabilized version of B-catenin? Is it likely that a mutation in caspase 9, B-cats, or CDk genes were involved in neocortical evolution?
Decreasing apoptosis or increasing rate of neural stem cell proliferation in VZ.
KO caspase 3/9 –> more NSC founder cells and RGS –> more radial columns –> more convolutions
Stabilized B-catenin develop an increased number of founder cells in VZ which leads to more radial columns and more convolutions.
Not likely involved in evolution bc these mice are not viable.
How do we theorize about the fact that the pattern of convolutions is highly reproducible within each species with relatively small individual variations?
Scientists have proposed a role for the long portico-cortical axonal tracts, which form distinct fascicles that crisscross through the voluminous intermediate zone (which eventually becomes subcortical white matter). The tension created by these fascicles is responsible for the stereotyped shape and orientation of the convolutions in gyrencephalic brains.
Explain the currently existing model of radial neuronal migration.
Cohorts of neurons generated in VZ traverse intermediate zone (eventually becomes subcortical white matter) and subplate zone (where afferents are ‘waiting’ from cortico-cortical connections, thalamic radiation, nucleus basalis, monoamine subcortical centres) and pass through earlier generated layers before settling at interface between cortical plate and marginal zone.
How is positional information of neurons generated in VZ preserved throughout cortical expansion?
By transient radial glial scaffolding.
LOOK INTO THIS DEEPER! not satisfactory.
Describe how radial glial cells might have diversified during evolution to accommodate the need (in humans and primates) to develop cerebral convolutions?
RGCs in humans/primates might have had an advantageous mutation which caused the to differentiate precociously (express GFAP at onset of corticogenesis), which means they are more stable and have greater longevity to form RG scaffolding in developing cortex to allow for neuronal migration along long and durable curvilinear radial glial migratory pathways. In mouse, mature radial glial markers are expressed only after birth.
In primate forebrain, many RGCs transiently stop dividing while their fibres span the entire cerebral wall, retaining their end feet at the ventricular and pial surfaces.
In primates, a single RGC fibre can accommodate up to how many simultaneously migrating neurons?
30!
