Wiring the brain Flashcards
What is the estimated number of neurons in the human brain?
The human brain contains approximately 85 billion neurons.
What are the three major stages of neuronal structure development?
- Cell proliferation
- Cell migration
- Cell differentiation
Describe the process of cell proliferation in neuronal development
- Neural progenitors, known as radial glial cells, divide to give rise to neurons and astrocytes.
- Radial glial cells undergo symmetrical cell division early in development, expanding the neural progenitor population.
- Later in development, they switch to asymmetrical cell division, with one daughter cell migrating to the cortex and the other remaining in the ventricular zone for further divisions
describe the “positions” of cell proliferation
- First position: A cell in the ventricular zone extends a process that reaches upward toward the pia.
- Second position: The nucleus of the cell migrates upward from the ventricular
surface toward the pial surface; the cell’s DNA is copied. - Third position: The nucleus, containing two complete copies of the genetic instructions, settles back to the ventricular surface.
- Fourth position: The cell retracts its arm from the pial surface.
- Fifth position: The cell divides in two.
When do the majority of neocortical neurons in humans get generated, and at what rate?
-The majority of neocortical neurons are generated between the fifth week and the fifth month of gestation (pregnancy).
-Neurons are generated at an astonishing rate of 250,000 new neurons per minute during this period.
What happens once a daughter cell commits to a neuronal fate in neuronal development?
Once a daughter cell commits to a neuronal fate, it will never divide again.
Is there ongoing neurogenesis (generation of new neurons) in most parts of the adult brain?
No, in most parts of the brain, the neurons you are born with are all you will have in your lifetime.
How is a cell’s fate determined?
Cell fate is determined by differences in gene expression during development, regulated by transcription factors.
What makes one cell different from another?
The specific genes that generate mRNA and proteins make one cell different from another.
What regulates gene expression in cells?
Gene expression is regulated by cellular proteins called transcription factors.
How can the cleavage plane during cell division affect cell fate?
If transcription factors or upstream molecules regulating them are unevenly distributed within a cell, the cleavage plane during cell division can determine which factors are passed on to daughter cells, influencing their fate.
What factors determine the ultimate fate of migrating daughter cells?
Factors including the age of the precursor cell, its position within the ventricular zone, and its environment at the time of division determine the ultimate fate of migrating daughter cells during cortical development.
From where do cortical pyramidal neurons and astrocytes derive?
Cortical pyramidal neurons and astrocytes derive from the dorsal ventricular zone.
From where do inhibitory interneurons and oligodendroglia derive?
Inhibitory interneurons and oligodendroglia derive from the ventral telencephalon.
What is the role of the subplate in cortical development?
The subplate is a layer where the first cells to migrate away from the dorsal ventricular zone reside, and it eventually disappears as development proceeds.
In what order do neurons of different cortical layers develop?
Neurons in cortical layers develop in the following order: subplate, layer VI, layer V, layer IV, layer III, and layer II.
How does primate cortical development differ from rodents?
Primates, like humans, have an additional proliferative layer of cells called the subventricular zone, which contributes to the development of the upper layers of the cortex (layers II–III) and plays a role in corticocortical connections. This difference contributes to the complexity of the primate neocortex.
How do many daughter cells migrate in the developing brain?
Many daughter cells migrate by slithering along the thin fibers emitted by radial glial cells that span the distance between the ventricular zone and the pia.
What are the immature neurons that follow radial paths from the ventricular zone toward the surface of the brain called?
The immature neurons are called neural precursor cells.
What happens when cortical assembly is complete?
When cortical assembly is complete, the radial glia withdraw their radial processes.
Do all migrating neural precursor cells follow the path provided by radial glial cells?
No, about one-third of the neural precursor cells wander horizontally on their way to the cortex.
Which type of neural precursor cells are among the first to migrate away from the ventricular zone?
The neural precursor cells destined to become subplate cells are among the first to migrate away from the ventricular zone.
How is the cortex assembled in terms of the order of cell migration?
First cells to migrate take up residence in
subplate layer, which eventually disappears. The cortex is assembled inside out, with the first cells to arrive in the cortical plate becoming layer VI neurons, followed by layer V cells, layer IV cells, and so on.
What gene mutation can disrupt the orderly process of cortex assembly?
Mutations in genes, such as the reelin gene, can disrupt the orderly process of cortex assembly. For example, in the reeler mutant mouse, neurons of the cortical plate are unable to pass through the subplate and pile up below it.
What is the process called when a cell takes on the appearance and characteristics of a neuron?
Cell differentiation.
What triggers cell differentiation in neural precursor cells?
Specific spatiotemporal patterns of gene expression
When does neuronal differentiation typically begin in the cortex?
Neuronal differentiation begins as soon as the neural precursor cells divide, with further differentiation occurring when they arrive in the cortical plate.
In what order do different types of brain cells, such as neurons, astrocytes, and oligodendrocytes, typically differentiate?
Neurons differentiate first, followed by astrocytes, and then oligodendrocytes.
What are the initial signs of neuronal differentiation in a neural precursor cell?
The appearance of neurites sprouting off the cell body.
Which structures in a differentiated neuron become recognizable as the axon and dendrites?
One of the neurites becomes recognizable as the axon, and the others become dendrites
Can neuronal differentiation occur outside of the brain environment, such as in tissue culture?
Yes, neuronal differentiation can occur even when the neural precursor cell is removed from the brain and placed in tissue culture.
What is responsible for the stereotypical architecture of cortical dendrites and axons in pyramidal neurons?
Intercellular signals, such as the protein semaphorin 3A, play a role in directing the growth of neurites and the formation of dendritic and axonal structures in pyramidal neurons.
What is the neocortex often compared to? How is the neocortex more accurately described in terms of structure?
A sheet of tissue. It’s like a patchwork quilt with distinct areas stitched together.
How are most cortical neurons formed and positioned during development?
They are born in the ventricular zone and migrate along radial glia to their final cortical layer
What does the concept of a cortical “protomap” propose?
t suggests that migrating neural precursor cells are guided precisely to the cortical plate by radial glial fibers.
What does the radial unit hypothesis suggest about cortical neurons’ birthplaces?
It suggests that neurons in an entire radial column of the cortex originate from the same ventricular zone birthplace
What contributes to the dramatic expansion of the human neocortex during evolution?
Differences in the duration of symmetrical cell division and an increase in the number of proliferative radial glial cells.
How do neural precursor cells find their final resting place in the developing neocortex?
Neurons in different regions of the cortex have distinct molecular identities, with unique transcription factors like Emx2 and Pax6. These factors create gradients along the anterior-posterior axis of the ventricular zone. Neurons with higher Pax6 levels migrate to the anterior neocortex, while those with more Emx2 head to the posterior cortex. Differences in transcription factors act as signals to guide neural precursor cells to their appropriate destinations.
What happens when mice are genetically engineered to produce less Emx2?
When mice produce less Emx2, there is an expansion of the anterior cortical areas like the motor cortex and a shrinkage of posterior cortical areas such as the visual cortex.
What is the consequence of knocking out Pax6 in mice?
Knocking out Pax6 in mice leads to an expansion of the visual cortex and a shrinkage of the frontal cortex.
What happened when researchers replaced the parietal cortex in newborn rats with a piece of occipital cortex?
Thalamic fibers from the VP nucleus invaded the new piece of cortex, assuming the cytoarchitecture characteristic of the rodent somatosensory cortex.
What did the experiment conducted by Schlaggar and O’Leary suggest about the role of the thalamus in cortical development?
It suggested that the thalamus is important for specifying the pattern of cortical areas.
How do subplate neurons contribute to the development of cortical areas?
Subplate neurons attract appropriate thalamic axons to different parts of the developing cortex, leading to cytoarchitectural differentiation when these axons invade the cortex.
What is the role of the subplate layer in the assembly of the cortical quilt during brain development?
The subplate layer of earliest born neurons appears to contain the instructions for the assembly of the cortical quilt, influencing the development of cortical areas
What are the three phases of pathway formation in the central nervous system (CNS)?
Pathway selection, target selection, and address selection
In the context of the development of the visual pathway, what does “pathway selection” refer to?
Pathway selection involves the decisions made by growing axons regarding which route to take, such as crossing over at the optic chiasm or staying on the same side.
What is “target selection” in pathway formation?
Target selection is the decision made by growing axons to innervate the correct thalamic nucleus, such as the lateral geniculate nucleus (LGN) in the visual pathway.
What is the significance of “address selection” in pathway formation?
Address selection involves ensuring that the axon reaches the correct layer of the LGN and establishes retinotopy, allowing for precise visual information processing.
How do neurons communicate during pathway formation?
Neurons communicate during pathway formation through direct cell–cell contact, contact with extracellular secretions, and communication via diffusible chemicals. As pathways develop, communication also occurs through action potentials and synaptic transmission.
What is the term for the growing tip of a neurite that identifies an appropriate path for neurite elongation?
Growth cone.
What are the flat sheets of membrane on the leading edge of the growth cone called?
Lamellipodia.
What are the thin spikes extending from the lamellipodia that constantly probe the environment called?
Filopodia.
What is the extracellular matrix?
Fibrous proteins deposited in the spaces between cells.
What type of molecules in the growing axons bind to laminin, promoting axonal elongation?
Integrins.
What is the mechanism that causes axons growing together to stick together?
Fasciculation.
What are the specific surface molecules in the membrane of neighboring axons that bind tightly to each other, causing axons to grow in unison?
Cell-adhesion molecules (CAMs).
How do pioneer axons contribute to the formation of neural pathways?
Pioneer axons establish initial connections and guide neighboring axons as the nervous system expands.
What is the role of intermediate targets in the growth of pioneer axons?
Intermediate targets serve as waypoints, and the interaction between axons and intermediate targets helps guide axons in the correct direction.
How are pioneer axon trajectories organized during growth?
Pioneer axon trajectories are divided into short segments, each ending at an intermediate target, ensuring precise growth along specific paths.
What is the significance of connecting the dots in axon growth?
By connecting intermediate targets, pioneer axons eventually reach their final destination in a highly organized manner.
What determines the direction and amount of growth in axons?
Interactions of cell surface molecules on growth cones with guidance cues in the environment.
What are chemoattractants, and how do they work in axon growth?
Chemoattractants are diffusible molecules that attract growing axons toward their targets. They act over a distance, much like the aroma of coffee attracting a coffee lover.
What is the first identified chemoattractant in mammals?
Netrin, a protein secreted by neurons in the ventral midline of the spinal cord.
How does netrin work to attract axons?
Netrin binds to its receptors on axons, spurring growth toward the source of netrin, creating a gradient.
