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Flashcards in Embryology of nervous system Deck (112)
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1
Q

What are the prosencephalon and mesencephalon and rhombencephalon?

A
  • Specializations along the rostro-caudal axis
    • Development centers at the rostral end of the neural tube
    • Primary cerebral vesicles
    • Go on to develop into five secondary cerebral vesicles
2
Q

How do each of the primary cerebral vesicles form the 5 secondary cerebral vesicles?

A

• Prosencephalic vesicle - segments from one into three
○ Telencephalic vesicles are paired vesicles cranially
○ They expand off of the more caudal diencephalic vesicle
• Mesencephalic vesicle - stays the same and does not further segment
• Rhombencephalic vesicle - splits into more cranial metencephalon and the more caudal myelencephalon

3
Q

The secondary cerebral vesicles and their lumens correspond to what adult nervous system components?

A

• Telencephalic vesicles
○ These are paired and they form the cerebral hemispheres, each with a lateral ventricle
• Diencephalic vesicle
○ Thalamus, hypothalamus, subthalamus, epithalamus
○ Lumen of vesicle will give rise to third ventricle which communicates with each lateral ventricle through the foramina of monroe
• Mesencephalic vesicle
○ Mesencephalon (midbrain)
○ Lumen - aqueduct of sylvius
• Metencephalon
○ Pons and cerebellum
○ Lumen of rhombencephalon will become 4th ventricle which communicates with subarachnoid space
○ Paired foramina of Luschka and midline foramen of Magendie
• Myelencephalon
○ Medulla
○ Lumen of rhombencephalon will become 4th ventricle which communicates with subarachnoid space
○ Paired foramina of Luschka and midline foramen of Magendie

4
Q

The lateral ventricles come from what?

A

• Lumen of telencephalic vesicles

5
Q

What are the names of the 5 secondary brain vesicles?

A
  • Telencephalon
    • Diencephalon
    • Mesencephalon
    • Metencephalon
    • myelencephalon
6
Q

What is the initial event that appears to establish the axis of the embryo?

A
  • Mammalian egg is symmetric, but sperm entry breaks symmetry
    • Blastomere getting the sperm entry point tends to divide first forming the embryonic pole
    • Rostrocaudal axis occurs with implantation, ICM side of blastocyst enters uterine wall
    • The end that leads implantation is the caudal end
7
Q

What are the early signalling events that helps the embryo grow along an axis?

A
  • Signal from implanting trophoblast (nodal) induces a head organizer in the anterior hypoblast cell
    • Secreted factor cerebrus inhibits nodal and creates a gradient of nodal signaling (rostrocaudal in orientation)
    • Forms primitive knot, hensens node/primitive node
8
Q

The primitive rod-like notochordal process is formed by what?

A
  • Portions of the primitive mesoderm coalescing and forming the notocordal process
    • This is just below the primitive node initially and grows caudally
    • This structure is initially hollow
9
Q

What is the “normal” destiny of the neurenteric canal?

A
  • It normally regresses and the notochord coalesces into a solid tube
    • However, this process and fail and cause a neurenteric fistula or neurenteric cyst
10
Q

What is the neurenteric canal?

A
  • The hollow notochordal process fuses with the endodermal layer
    • As this fusion occurs there is a brief period of time where the amniotic cavity and yolk sac are in communication through the notochordal process
    • The communication is called the neurenteric canal
11
Q

The release of Sonic Hedgehog is due to what structure and what is the result?

A
  • The notochord releases Shh
    • Induces the overlying ectoderm to divide rapidly
    • Forms a thickened cell mass called the neural plate
    • Neural plate will then crease and form neural groove
    • Eventually the groove will become a tube, which becomes the adult nervous system
12
Q

What are the anterior and posterior neuropores?

A
  • The small unroofed portions or openings at each end of the neural tube
    • Part of the lengthening of the neural tube is when the neural folds come together in a “zipper like” fashion, progressing rostrocaudal toward each end
    • The “zippering” doesn’t quite finish and that results in the two ends having neuropores
    • The do eventually close as well
13
Q

When does secondary neurulation take place?

A
  • 28-32 days
    • Aggregate of undifferentiated cells at caudal end of embryo (caudal cell mass) develops
    • It develops vacuoles as it enlarges
    • Ultimately makes contact with central canal of neural tube from primary neurulation
    • Caudal cell mass gives rise to conus medullaris and filum terminale
14
Q

What is a NTD less severe than a myelomeningocele but caused by the same general proces?

A
  • Lack of a vertebral arch in a given area
    • The neural tube does close but it is not completely surounded by the sclerotome
    • The sclerotome makes up the vertebral arch, so that doesn’t form
    • Usually there is a mark in the skin or a dimple where this lack of fusion took place
15
Q

What went wrong if there is a myelomeningocele?

A
  • Incomplete closure of the neural tube

* Plaque of neural tissue contiguous with epidermis

16
Q

Where do the adult structures: conus medullaris and filum terminale come from in the embryo?

A

• The caudal cell mass of secondary neurulation

17
Q

What might cause the failure of forebrain structures to develop?

A
  • This is called anencephaly
    • The neural tube does not close at the anterior neuropore
    • The neuropores are the last areas in the “zippering” of the nerual tube to fully fold over and close
18
Q

What dietary intervention has been key in reducing neural tube defects?

A
  • Periconceptional folic acid supplements
    • 400 micrograms of folic acid daily through the first trimester of pregnancy
    • If they have previously had a NTD pregancy then 4mg daily 1 month before conception is recommended
19
Q

What is a key molecular mechanism to determining an axis upon which the embryo devleops?

A
  • A concentration gradient of morphogens secreted by anterior cells vs. posterior cells
    • The concentration gradient gives rise to regional expression of different developmental control genes along the axis of the morphogen gradient
    • Wnts, FGFs and retinoic acid are the major players for the AP/RC axis
20
Q

What are the important morphogens for the development of the AP/RC axis?

A
  • Wnts, FGFs and retinoic acid are the major players for the AP/RC axis
    • Cerebrus and dickkopf are secreted by the anterior visceral endoderm and they promote forebrain differentiation
21
Q

What factors, when secreted, promote forebrain differentiation?

A

• Cerebrus and dickkopf are secreted by the anterior visceral endoderm and they promote forebrain differentiation
*this is happening in the context of the RC/AP axis being developed in the embryo

22
Q

What are the names of genes that are super fundamental in AP patterning of nervous tissue?

A
  • Homeobox genes
    • First discovered in Drosophila embryonic patterning
    • Best characterized in development of rhombencephalon
23
Q

What are rhombomeres?

A
  • 8 morphologically distinct elements within the developing rhombencephalon
    • They are repeating units that end up differentiating similarly, but distinct based on region
    • Under the main control of homeobox genes
    • Between rhombomeres, cells will differ in terms ofmorphology, axonal trajectories, NT synthesis, NT selectivity, firing properties and synapse specificity
24
Q

What is the result of Hox gene expression varying along the AP axis of the neural tube?

A
  • The result is a differential gene expression pattern overall in the different rhombomeres
    • The programs of differentiation they trigger will vary according to position along axis
25
Q

What is RA, and what are RAREs?

A
  • RA is retinoic acid, a vital secreted factor for the deveolpment of the AP axis in neural development
    • RA is membrane permeant and bindes to RARs or Retinoic acid receptors
    • The receptors will invfluence gene expression along RA response elements in the DNA, or RAREs
    • RA is highest in concentration around the posterior positions
    • Too much RA means too much posterior structures at the expence of anterior ones
    • Thus, RA can toxicity can mess up the embryo something fierce
26
Q

What is the neuroepithelial layer?

A
  • The walls of the neural tube initially possess a pseudostratified layer of primitive ectoderm known as the neuroepithelial layer
    • Though uniform initially, it develops differently in the different RC sections
    • This layer will eventually form nearly all of the cellular elements of the CNS
    • Except for microglia which come from the reticuloendothelial system
27
Q

What pattern of movement do the dividing cells within the neuroepithelial layer have?

A
  • They oscillated between inner and outer walls
    • The process of mitosis happens when they are near the inner wall
    • They move back to the outer wall to start going through S phase
    • The result is thickening of the walls of the neural tube and enlargements of vesicles at the anterior end
    • Some will become neurons, others glial cells
28
Q

In the neuroepithelial layer, what keeps the cells within the inner and outer walls?

A
  • Cell bodies shift along their processes
    • There are cell processess attached to the inner and outer walls and the cell bodies move out or in depending on what phase in the cell cycle they are
    • Daughter cells can make their own processes OR they can lose them and end up being primed for migration
29
Q

What’s up with the radial glial guide cells?

A
  • As the walls of the neural tube are rapidly thickening, cells are moving between the inner and outer walls a lot
    • Some of the glial cells form a rope ladder configuration along which primitive nerve cells can migrate
    • Becomes necessary as the migration distance gets longer and longer
30
Q

Where in the rapidly thickening walls of the neural tube is the growth the largest and the distance travelled the greatest?

A
  • The telencephalon, which is becoming the cortex where most of the higher level of mental activity occurs
    • It is made up of 6 cell layers and each layer is distinct in pattern of organization and connections
    • Initially the cells migrate in and form the deepest, or 6th layer
    • Each progressive migration forms a more superficial layer
    • Think of an inside out sequence of devleopment where each new layer has to move through the deeper one
31
Q

How is the “inside-out” migration scheme responsible for the different architecture of white vs. grey matter in the cortex vs. spinal cord?

A
  • Unlike the spinal cord, where cells proliferate around the ventricular zone then send their axons out toards the periphery (grey matter centrally, white matter outward)
    • The cells of the cortex migrate outwards, become established then send their axons and meyelin IN, forming a shell of grey matter and tracts of white matter diving deeper
32
Q

Instead of the RC axis being super important, what axis seems to decide the fate of spinal cord neurons?

A
  • The DV axis
    • Those progentior cells closer to ventral aspect will become motor neurons
    • Some of these will connect with the myotomes (thus innervate muscles)
    • The progenitor cells in the dorsal regions will be sensory, receiving inputs from cells of the DRG (which themselves come from the neural crest)
33
Q

What is the sulcus limitans?

A
  • A crease in the neural tube in the developing spinal cord area
    • Separates the ventral from dorsal population of neural progenitor cells
    • Ventral - basal plate
    • Dorsal - alar plate
34
Q

What are the basal and alar plates?

A
  • A crease in the neural tube in the developing spinal cord area
    • Separates the ventral from dorsal population of neural progenitor cells
    • Ventral - basal plate
    • Dorsal - alar plate
35
Q

What are the most important morphogens involved in dorsoventral patterning?

A
  • Shh = sonic hedgehog (initially secreted by the notochord)

* BMPs - secreted by lateral ectoderm

36
Q

What’s up with BMP signaling in the context of dorsoventral patterning?

A
  • Initially BMP permeate the entire flat embryonic disc
    • Secretion of BMP inhibitors by midline primitive node and notochord give rise to a BMP poor medial zone
    • Thus pushing cells to commit to midline structures including the neural plate
    • BMP rich lateral aspects make up the dorsal arch as the neural tube folds and zippers
    • Shh and BMP spatial differences help establish dorsoventral axis
37
Q

How is the cortex given its dorsoventral axis?

A
  • Before the telencephalic vesicles begin to form, the rostral neural tube develops regionally restricted DV markers
    • This creates three discrete proliferative zones
    • Cortex - most dorsal
    • Lateral and medial ganglionic eminences (in the middle)
    • Basal forebrain - most ventral
38
Q

What is the result of the telencephalic vesicle folding over itself?

A

• Formation of the sylvian fissure (lateral sulcus)
• Also buries a patch of cortex within the fissure producing the insular cortex
• The lateral ventricle associated with the telencephalic vesicle is distored into a C shape
• The caudate nucleus is also distorted into a C shape
○ Portion of the gray matter derived from the lateral ganglionic eminence
• The telencephalon structures follow the C shape, and coronal planes will cut through these structures twice

39
Q

What are the putamen and globus pallidus?

A
  • Separated structures by axons emanating from neurons in the cortex which are descending to multiple targets
    • They are components of the basal ganglia
    • The caudate nucleus is the medial basal ganglia structure
    • These are from the telecephalon
40
Q

The third ventricle comes from what?

A

• Diencephalic vesicle (lumen)

41
Q

In what form does the nervous system begin?

A
  • Flat epithelium called the neurectoderm
    • This will round up and form the neural tube
    • Formation of the neural tube marks the beginning of neurogenesis
42
Q

When the ventricular walls are being developed (neurogenesis) where are the cell bodies of the precursor cells when they are in S phase?

A
  • Most superficial, or furthest from the inner ventricular wall
    • Cell division happens when the cell body is closest to the ventricle, or the inner wall
43
Q

What are the regions in which proliferating cells are found? (neurogenesis)

A
  • Ventricular zones that are the layer closes to the neural tube lumen/ventricle
    • Or central canal in the case of the spinal cord
    • Dividing cells have processes that attach medially to the ventriclular surface and laterally to the external surface (processes connecting them to the walls of the ventricle)
44
Q

What is the method most used to study neurogenesis?

A
  • Labeling dividing cells with detectable DNA precursors
    • H3-thymidine or bromodeoxyuridine
    • Cells take up labeled DNA building blocks during S phase
    • A cell’s birthdate is defined as the time it undergoes its last round of DNA synthesis (S phase)
45
Q

Once a progenitor cell divides close to the ventricular surface, what choice does it have to make?

A
  • It can re-establish it’s connection to the outer ventricular wall or it can lose it’s inner wall connection
    • Re-establishment means it goes through another round of moving and then dividing
    • Losing the connections makes it a post-mitotic neuron with it’s birthdate the last S phase it went through
46
Q

Describe the progenitor cells that are going through M phase in early neurogenesis

A
  • One of their processes has detached from the external wall of the ventricle (the most superficial wall)
    • It maintains it’s connection to the inner wall
    • The cell body is very close to the ventricular surface (inner wall)
47
Q

When, relative to birth, does neurogenesis occur?

A
  • MOST regions have the majority of neurogenesis occur prior to birth
    • Cerebellum is postnatal (granule neurons)
    • Many olfactory and hippocampal neurons are postnattaly developed as well
48
Q

What are secondary zones of neurogenesis?

A
  • Hot spots of postnatal neurogenesis
    • Cerebellum - external granule layer
    • Start out in a layer around the 4th ventricle (ventricular zone)
    • They migrate over the purkinje cells and form the neurogenic region (external granule layer, an example of a secondary zone of neurogenesis)
    • When they exit the cell cycle they migrate into the cerebellum
    • Happens until year 2 postnatal
49
Q

What is the secondary zone of neurogenesis for olfactory neurons?

A
  • The subventricular zone
    • Original precursor cells are here, but they migrate to another place to begin dividing prior to exiting the mitotic cycle
    • For olfactory, the cells start out right next to the lateral wall of the lateral ventricles
    • Migrate not very far laterally to begin division
    • Post-mitotic cells migrate anteriorly and rostrally to form olfactory bulb
50
Q

What characteristics do secondary zones of neurogenesis share?

A
  • Arise in ventricular zone
    • Migrate before exiting mitotic cyle to a new non-ventricular location
    • Proliferate postnatally in non-ventricular zone locations and then often have a little post-mitotic migration as well
51
Q

What are the 3 secondary zones of neurogenesis that were covered?

A
  • External granule layer
    • Subventricular zone
    • Dentate gyrus
52
Q

Where do hippocampal precursors start out and migrate to?

A
  • Progenitors are in the ventricular zone

* Migrate to developing dentate gyrus and form their proliferation center

53
Q

What phenomenon seems to determine if a dividing precursor will keep its appendages and keep dividing or stop and migrate?

A

• The plane of cleavage
• Perpendicular to ventricular surface = keep attachments and majority of daughter cells stay in division cycle
• Parallel to ventricular surface = lose attachments and migrate
○ One of the daughters stays bu the other does not
○ Asymmetrical division

54
Q

What do the genes prospero, numb and miranda have in common?

A
  • Genes that encode asymmetrically localized factors and play a role in cell fate decisions
    • Parallel vs. perpendicular planes of cleavage in neurogenesis
55
Q

What is shared unequally between daughter cells that furthers assymmetry?

A
  • Differential inheritance of cytoplasmic proteins, mRNAs and other factors
    • Thus in a parallel to the ventricular surface cleavage event one daugher cell keeps its attachments and goes through another round of division while one stops and migrates
    • In the dividing cell, the cytoplasm is purposefully organized so that plane of cleavage can decide cell fate
56
Q

What are the zones of migration in the early cerebral cortex?

A
  • Preplate - PP
    • MZ - marginal zone
    • CP - cortical plate
    • IZ - intermediate zone
    • SP - subplate
    • Deep ventricular zone with proliferating cells
57
Q

What is special about the subplate neurons?

A
  • Play pioneering roles in circuit formation

* Many will die early once they have played their roles and thus are considered a transient neuronal population

58
Q

What is the preplate?

A
  • PP, about 8-9 weeks embryogenesis
    • First neurons to become postmitotic migrate a distance of several cell bodies and form this new region called the preplate
    • Preplate will divide into the zones of cerebral cortex formation
59
Q

What cells act as guides for migrating neuron precursors after the preplate is formed?

A

• Radial glia - specialized glia that keep their processes and act like a rope ladder

60
Q

What are the 3 distinct stages in neuronal migration for the cerebral cortex?

A
  • Onset of migration
    • Ongoing migration
    • Migration stop
    • You can have disorders with each of these processes/steps
61
Q

What is an example of a disease that affects the onset of neuronal migration?

A

• PH = periventricular heterotopia
• In PH, neurons can’t leave ventricular zone so they just differentiate too deep
• PH has an X-linked dominant inheritance
• Males with affected X-chromosome do not typically survive to term
• PH females typically have epilepsy without cognitive abnormalities
*cytoskelatal gene FLNA (filaminA) is mutated

62
Q

What can go wrong in the first step of migration?

A
  • Onset of neuronal migration
    • FLNA - filaminA gene mutations can result in PH = periventricular heterotopia
    • FLNA - actin-binding crosslinking protein which messes with movement through cytoskelatal problems
    • In PH, neurons can’t leave ventricular zone so they just differentiate too deep
    • PH has an X-linked dominant inheritance
    • Males with affected X-chromosome do not typically survive to term
    • PH females typically have epilepsy without cognitive abnormalities
63
Q

What are the two proteins implicated in messing up the second stage of migration?

A
  • Second stage = migration process/continuted migration
    • DCX = doublecortin - leads to double cortex syndrome
    • LIS1 = lissencephaly type one
64
Q

What’s up with type I lissencephaly?

A
  • Means smooth brain. Problem with migration
    • LIS1 is the protein, on chromosome 17
    • Need two healthy copies to be normal. One mutated copy presents with a phenotype
    • Leads to a lack of layer specificity. Migrating neurons pop off the “rope ladder” too soon
65
Q

What is the function of the DCX gene?

A
  • Neurons express DCX as they migrate

* Encodes a protein that colocalizes with microtubules and is thought to be a microtuble organizer

66
Q

What’s up with double cortex syndrome?

A
  • DCX is the mutated gene
    • Found on X-chromosome
    • Affected males resemple the lissencephaly phenotype
    • Females with one affected X will have double cortex syndrome
    • Epilepsy, mild mental retardation and subcortical band heterotopia
    • X-linked inheritance
67
Q

What are the 4 mouse genes that affect the stopping of migration?

A
  • These 4 genes apparently help migrating neurons pop off the radial glia
    • Reeler
    • Dab1
    • Mldlr
    • Apoer2
68
Q

What is the human version (disease) of the reeler mouse phenotype?

A
  • LCH - lissencephaly with cerebellar hypoplasia

* Defect in alternative splicing and a frame shift mutation with truncated protein

69
Q

The products of the Vldlr and Apoer2 genes do what?

A
  • They are reelin receptors, which are on the migrating neurons.
    • If they bind reelin that helps them pop off the radial glia
    • Apoer2 is cerebral, Vldlr is cerebellar
70
Q

What is Reelin and when is it expressed?

A
  • Large extracellular protein
    • Expressed by cells that are transiently present during embryogenesis in the marginal zone and preplate
    • Cajal-Retzius cells
    • Plays a role in the decision of a cell to stop migrating
71
Q

What does the reeler gene do?

A
  • Reelin protein, mutation result in reversal of inside-out cortical pattern
    • Accumulation of neurons in the superficial marginal layer
    • Cerebellar problems with mutation - purkinje cells do not form a well-defined layer but distribute in aggregates
    • Affects gait
72
Q

What is the general principle of neurogenesis to keep in mind?

A
  • It really matters when an neuron progenitor is born
    • Neurons born at the same time tend to end up together in the same layer and follow similar programs of differentiation
73
Q

What is an alternative migration pattern to radial migration?

A
  • Tangential migration
    • Results in progeny of a single progenitor being dispersed throughout a particular tissue
    • Notable example = inhibitory GABA-containing cells in the cerebral cortex
74
Q

What happens when a developing neuron gets to it’s final migratory destination?

A
  • Usually interacts with other neurons to form a distinct nucleus or layer
    • Tend to aggregate with other like neurons expressing cell surface markers that are “like” to themselves
    • Gradients of surface markers likely are maps that guide CNS development
75
Q

What is the pattern of migration some cells use to get to the olfactory bulb called?

A
  • Rostral migratory stream

* Chain migration

76
Q

In terms of migration, what is the difference (typically) between pyramidal cells and GABA containing cells?

A
  • Remember pyramidal cells are glutamate-containing cells (excitatory)
    • GABA neurons migrate tangentially
    • Pyramidal neurons migrate radially
77
Q

Where do GABA containing cells originate?

A

• Migrate tangentially from portions of the ventricular zone in ventral forebrain gregions known as the lateral and medial ganglionic eminences

78
Q

Where do the neural crest cells originate?

A
  • Arise from the boundary region between the neurectoderm and epidermis
    • After neural tube closure, the neural crest is a mass of cells on top of the dorsal tube
79
Q

When neural crest cells are expressing cadherin, what is likely the case?

A
  • They express cadherin when they are done migrating.

* Thus, these neural crest cells have likely reached their final destination

80
Q

What are the two paths of neural crest migration?

A
  • Dorsal (lateral) stream - pigment cells
    • Ventral stream - flows ventromedially and dives under dorsal dermamyotomes and gives rise to sensory, autonomic and enteric ganglia
81
Q

What seems to be the molecular mechanism of guiding neural crest migration?

A
  • Permissive vs. non-permissive surfaces
    • Decided by the expression of cell-surface markers and ECM secreted proteins
    • Laminin and fibronectin are permissive
    • Other cells express surfaces that discourage neural crest migration
82
Q

What structures come from the neural crest cells?

A
  • Peripheral nervous system
    • Pigment cells
    • Cartilage
    • Sensory ganglia
    • Enteric nervous system
83
Q

What is the neurotrophic hypothesis

A
  • Deals with apoptosis in neural development
    • Targets provide limiting amounts of nutrient or trophic factor that is taken up by input nerve terminals
    • Essentially the final destination decides the number and type of neurons it want/needs
84
Q

What are the given examples of neurotrophic factors?

A
  • Promote cell survival
    • NGF - nerve growth factor
    • BDNF - brain derived neurotrophic factor
    • NT-3 (neurotophin-3)
    • NT-4/5 (neurotrophin-4/5)
    • CNTF - interleukin class with leukemia inhibitor factor (LIF) and cardiotropin
85
Q

What does mutation of BDNF gene result in? (general)

A

• Hippocampal function and memory formation problems

86
Q

Neurotrophic factors generally do what?

A
  • Inhibit apoptosis

* As soon as they are not present the cells involved usually die off

87
Q

NGF is important as a trophic factor for what class of neuron?

A
  • Sensory and autonomic neurons, but not CNS

* CNS neurons don’t seem to have a “one major factor” but they instead require multiple concurrent signals for survival

88
Q

What happens intracellularly when a Trk binds a neurotrophin?

A
  • Trk receptors act like other receptors (receptor tyrosine kinase) in that there is dimerization, phosphorylation and recruitment of signaling cascade machinery
    • Ras, PI3 kinase and PLC
89
Q

What class of receptors bind neurotrophins?

A
  • Tropomyosin-related kinase family
    • Trk’s
    • Each neurotrophin has a favorite receptor or spread of receptors and vice versa
90
Q

Neurotrophins have what function beyond a survival signal for neurons?

A
  • They play a permissive role in axonal growth
    • They induce programs of differentiation that are required for the formation of axons and dendrites
    • Add neurotrophins to cultured cells and they form initial processes
    • Permissive role, not involved in axonal pathfinding
91
Q

What is up with the oligophrenin-1 protein?

A
  • Modulates the activity of an enzyme that regulates the cytoskeleton
    • Can result in mental retardation in mutated
92
Q

What is axonal pathfinding?

A
  • The process of the axon growth cone growing into the environment and ending up connecting to something important
    • Membrane, cytoskelatal proteins and other components are needed to sniff out the proper direction
    • Growth cone sprouts filopodia which have certain receptor populations that guide further growth
93
Q

What are the long-range guidance molecules?

A
  • Netrins and semaphorins
    • Semaphorins can only be repulsive
    • Netrins can be repulsive or attractive depending on the rereceptor it binds
94
Q

What are the short-range guidance molecules?

A
  • Cadherins and cell adhesion molecules (CAMs) on the cell surface - attractive
    • Collagen, laminin, fibronectin and proteoglycans in the ECM - attractive
    • Semaphorins, ephrins (cell surface) - replusion
    • Tenascin (ECM) - repulsion
95
Q

What would the binding of a cadherin do?

A
  • Cadherins bind other cadherins

* Result in calcium dependent adhesion and outgrowth of axon

96
Q

What happens when eph kinases bind their ligand?

A
  • Eph kinases bind ephrins
    • Result is chemorepulsion
    • Eventually the topgroaphic map is formed by densities of receptor and ligand (visual system)
97
Q

What happens when neuropilins and plexins bind their ligand?

A
  • Neuropilins and plexins bind semaphorins

* Results in chemorepulsion of axonal growth cone

98
Q

What does the DCC receptor bind?

A
  • Netrins
    • Chemoattraction or repulsion
    • Midline crossing
    • Intracellular cAMP levels will drive the strength of the response
99
Q

When you see alpha4-beta1 receptors, think what?

A
  • Collagens, fibronectin, etc

* Binding ECM components for local attraction and repulsion of growing axon

100
Q

What would binding of integrins do?

A
  • Integrins are the receptors for ECM moleules

* Result in local attraction and repulsion

101
Q

Axonal regeneration in the adult CNS deals with what three factors?

A
  • Ability of axons to grow
    • Presence of molecules to promote growth
    • Presence of molecules and receptors that inhibit growth
102
Q

What is the key experiment described (1996) that used the three principles of axonal regeneration?

A
  • Implantation of a peripheral nerve in an experimentally transected spinal cord
    • Regained some function
    • Bathed implant in FGF
    • Peripheral nerve, so the glia was schwann cell
103
Q

What factors promote axonal regeneration

A
  • NGF - produced by schwann cell

* FGF = fibroblast growth factor - also promotes axonal growth

104
Q

What might inhibit axonal regeneration in the adult CNS?

A
  • Nogo, epressed by myelin

* Binds - Nogo66 receptor and seems to be a secreted factor that keeps CNS from regenerating much

105
Q

What function of the neuron seems to play an important role in synapse elimination?

A
  • Electrical activity
    • Correlated firing of pre and post-synaptic cells favors selective synapse stabilization
    • Asynhronous firing of inputs and target promote synapse elimination
106
Q

The postsynaptic cell plays into synapse stabilization how?

A
  • By secreting a neurotrophin or similar substance
    • Pre-synaptic terminals that are retained have somehow preferentially taken up post-synaptically released neurotrophin or neurotrophin-like substance
107
Q

When you see trkB and epilepsy in the same sentence what should you think?

A
  • This is an example of neurotrophins modulating the activity/efficacy of a synapse
    • BDNF is the neurotrophin, trkB is the receptor
    • Looked at in the treatment of epilepsy
108
Q

In terms of cortical dendritic spines, what is indicative of Down’s Syndrome vs. normal?

A
  • Normally, during the first postnatal year the density of cortical dendritic spines increases as dendritic spines thicken
    • In DS, dendritic spines are abnormally thin and short
    • This may reflect abnormal pruning or synapse maturation
109
Q

When does myelination occur?

A
  • Begins during embryonic stages
    • First present in periphery
    • CNS, meylination is first observed in the spinal cord near the end of the first trimester
    • By third trimester, myelination is in the brain
    • Several cortical tracts are myelinated after birth (those in higher level functions)
    • Corticospinal tract is myelinated after birth as well
110
Q

How do NT receptors contribute to development?

A
  • In different phases of development GABA receptors are made up of different subunits
    • The Ecl changes based on the subunit composition
    • There are embryonic forms of the channels and adult forms of the channels
    • During developmental stages, intracellular levels of chloride are elevated and thus there is a more depolarized value for Ecl
    • Thus GABA can lead to excitation
111
Q

Why does the neonatal brain have a lower seizure threshold?

A

• GABA receptors can actually lead to EPSPs because of their developmental subunit compostions

112
Q

Dab1 is important for stopping migration how?

A
  • It is an intracellular signalling chain component for the reelin:Apoer2 signaling chain
    • Still important for the decision to come off the radial glia

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