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NROD63H3 Lecture Notes - Basal Lamina, Posterior Grey Column, Occipital Lobe

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Chapter 23- Wiring the Brain
All retinal ganglion cells extend axons into the optic nerve, but only ganglion cell axons from the
nasal retinas cross at the optic chiasm
Axons from the two eyes are mixed in the optic tract, but in the lateral geniculate nucleus (LGN),
they are sorted out again:
oBy ganglion cell type
oBy eye of origin (ipsilateral or contralateral)
oBy retinotopic position
LGN neurons project axons into the optic radiations that travel via the internal capsule to the
primary visual cortex, here, they terminate
oOnly in cortical area 17
oOnly in specific cortical layers (mainly layer IV)
oAgain according to cell type and retinotopic position
The neurons in layer IV make very specific connections with cells in other cortical layers that are
appropriate for binocular vision and are specialized to enable the detection of contrast borders
Most of the wiring in the brain is specified by genetic programs that allow axons to detect the
correct pathways and the correct targets
oHowever, a small but important component of the final wiring depends on sensory
information about the world around us during early childhood
The Genesis of Neurons
First step in wiring the nervous system together is the generation of neurons
In the primary visual cortex (striate cortex), in the adult there are six cortical layers, and the
neurons in each of these layers have characteristic appearances and connections that distinguish
striate cortex from other areas
Neuronal structure develops in three major stages:
oCell proliferation
oCell migration
oCell differentiation
Cell Proliferation
Recall, the brain develops from the walls of the five fluid-filled vesicles
oThese fluid-filled spaces remain in the adult and constitute the ventricular system
Very early in development, walls of the vesicles consist of only two layers:
oVentricular zone and the marginal zone
The ventricular zone lines the inside of each vesicle, and the marginal zone faces the overlying pia
Within these layers of the telencephalic vesicle, a cellular ballet is performed that gives rise to all
the neurons and glia of the visual cortex
Choreography of cell proliferation
oFirst position: A cell in the ventricular zone extends a process that reaches upward toward
the pia
oSecond position: The nucleus of the cell migrates upward from the ventricular surface
toward the pial surface; the cell’s DNA is copied
oThird position: the nucleus, containing two complete copies of the genetic instructions,
settles back to the ventricular surface
oFourth position: The cell retracts its arm from the pial surface
oFifth position: The cell divides into two.
Fate of the newly formed daughter cell depends on a number of factors
A ventricular zone precursor cell that is cleaved vertically during division has a different fate than
one that is cleaved horizontally
After vertical cleavage, both daughter cells remain in teh ventricular zone to divide again and
oThis mode of cell division takes place in early development to expand the population of
neuronal precursors
Later in development, horizontal cleavage is the rule
In this case, the daughter cell lying farthest away from the ventricular surface migrates away to
take up its position in the cortex, where it will never divide again
The other daughter remains in the ventricular zone to undergo more divisions
Ventricular zone precursor cells repeat this pattern until all the neurons and glia of the cortex have
been generated
Once a cell commits to a neuronal fate, it will never divide again
How does cleavage plane during cell division determine the cell’s fate?
oAll of our cells contain the same complement of DNA inherited from our parents, so every
daughter cell has the same genes
oThe factor that makes one cell different from another is the specific genes that generate
mRNA and ultimately protein
oCell fate is regulated by differences in gene expression during development
oGene expression is regulated by cellular proteins called transcription factors
Multiple cell types, including neurons and glia, can arise from the same precursor cell
Neural stem cells- ability of the cell to give rise to many different types of tissue
Ultimate fate of the migrating daughter cell is determined by a combination of factors, including
the age of the precursor cell, its position within the ventricular zone, and its environment at the
time of division
Cortical pyramidal neurons and astrocytes derive from the dorsal ventricular zone, whereas
inhibitory interneurons and oligodendroglia derive from the ventral telencephalon
Subplate- consists of the cells that are the first to migrate away from the dorsal ventricular zone
oThe subplate eventually disappears as development proceeds
Next cells to divide become layer VI neurons, followed by the neurons of layers V, IV, III, and II
Cell Migration
Many daughter cells migrate by slithering along thin fibers that radiate from the ventricular zone
toward the pia
oThese fibers are derived from specialized radial glial cells, providing the scaffold on which
the cortex is built
Immature neurons called neuroblasts, follow this radial path from the ventricular zone toward the
surface of the brain
Some neurons actually derive from radial glia
oIn this case, migration occurs by the radial movement of the soma within the fiber that
connects the ventricular zone and pia
When cortical assembly is complete, the radial glia withdraw their radial processes
Not all migrating cells follow the path provided by the radial glial cells
o1/3 of the neurobalsts wander horizontally on their way to the cortex
Neuroblasts destined to become subplate cells are among the first to migrate away from the
ventricular zone
Neuroblasts destined to become the adult cortex migrate next
oThey cross the subplate and form another cell layer called the cortical plate
First cells to arrive in the cortical plate are those that will become layer VI neurons
Next come the layer V cells, followed by layer IV cells, and so on
oNotice that each new wave of neuroblasts migrates right past those in the existing cortical
In this way, the cortex is said to be assembled inside-out
This orderly process can disrupted by a number of gene mutations
Cell Differentiation
The process in which a cell takes on the appearance and characteristics of a neuron is called cell
Differentiation is the consequence of a specific spatiotemporal pattern of gene expression
As seen, neuroblast differentiation begins as soon as the precursor cells divide with the uneven
distribution of cell constituents
Neuronal differentiation occurs when the neuroblast arrives in the cortical plate
oThus layer V and VI neurons have differentiated into recognizable pyramidal cells even
before layer II cells hav migrated into the cortical plate
oNeuronal differentiation occurs first, followed by astrocyte differentiation that peaks at
about the time of birth
oOligodendrocytes are the last cells to differentiate
Differentiation of the neuroblast into a neuron begins with the appearance of neurites sprouting off
the cell body
oAt first these neurites are indistinguishable, but later they are visible to be the axons and
Differentiation will occur even if the neuroblast is removed from the brain and placed in tissue
oFor ex. Cells destined to become neocortical pyramidal cells will often assume the same
characteristic dendritic architecture in tissue culture
Therefore differentiation is programmed well before the neuroblast arrives at its final
resting place
However, stereotypical architecture of cortical dendrites and axons also depends on intercellular
Pyramidal neurons are characterized by a large apical dendrite that extends radially toward the
pia, and an axon that projects in the opposite direction
Differentiation of Cortical Areas
Most cortical neurons are born in the ventricular zone and then migrate along radial glia to take up
their final position in one of the cortical layers
It is reasonable to conclude that cortical areas in the adult brain simply reflect an organization that
is already present in the ventricular zone of the fetal telencephalon
The thalamus is important for specifying the pattern of cortical areas
How did the appropriate thalamic axons come to lie in wait under the parietal cortex in the first
oSubplate neurons, which have a more strictly radial migration pattern, attract the
appropriate thalamic axons to different parts of the developing cortex: LGN axons to
occipital cortex, VP nucleus axons to parietal cortex and so on
oArea-specific thalamic axons initially innervate distinct populations of subplate cells
The Genesis of Connections
As neurons differentiate, they extend axons that must find their appropriate targets
Think of this development of long-range connections, or pathway formation, in the CNS as
occurring in three phases: pathway selection, target selection, and address selection
There are different types of decisions that must be made for a growing axon:
oPathway selection
oTarget selection
oAddress selection
Three phases of pathway formation depends critically on communication between cells
Communication occurs in several ways:
oDirect cell-cell contact
oContact between cells and the extracellular secretions of other cells
oCommunication between cells over a distance via diffusible chemicals
The Growing Axon
Growth cone- growing tip of a neurite
Growth cone is specialized to identify an appropriate path for neurite elongation
The leading edge of the growth cone consists of flat sheets of membrane called lamellipodia that
undulate in rhythmic waves
Extending from the lamellipodia are thin spikes called filopodia, which constantly probe the
environment, moving in and out of the lamellipodia
Growth of the neurite occurs when a filopodium, instead of retracting, takes hold of the substrate
(the surface on which it is growing) and pulls the advancing growth cone forward