| Bergles (Astrocytes, NT transporters, presynaptic inhibition & retrograde signals) | Doetzlhofer (Neural Patterning) | Zhou (Regeneration) & Nathans (Engineering Principles) | Lee (iPSCs) | Blackshaw (Cell Fate Specification) |
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Cannabioid–dependent retrograde presynaptic inhibition
How do postsynaptic cells affect NT release from presynaptic cells?
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Cell fate is specified in a cell position-dependent manner by localized production of a morphogen
What does the French flag model represent?
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Action potential; will not lose information over long distances
What is an example of a digital (discrete) mechanism for processing information in the nervous system? Name one advantage.
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Mertens et al. decided to differentiate iPSC into hippocampal neurons, because Bipolar patients show reduced number of hippocampal neurons.
Give an example where the cell of interest is important to consider.
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[See PPT]
Which cell is most likely to show higher Notch signaling? (See PPT)
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[See PPT]
Describe stoichiometry and why it is important for transporter functions.
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Shh
What molecule “ventralizes” the spinal cord?
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Membrane potential
What is an example of an analog (continuous) mechanism for processing information in the nervous system?
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What is
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Activated astrocytes undergo intracellular calcium oscillations that can spread to adjacent astrocytes via ATP release and gap junction signaling, information which is propagated through the pan glial syncytium.
What is a calcium wave?
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M1 develops in Pax6+ area
What is the significance of Pax6 in the development of the neocortex?
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1. Glial scar proteins
a. CSPGs – chondroitin sulfate proteoglycans. Proteins with glycosaminoglycan chains (GAG), which primarily inhibit regeneration. 2. Myelin associated inhibitory factors a. Nogo – inhibits neurite outgrowth. b. MAG (myelin associated glycoprotein) – immunoglobulin superfamily member that normally promotes the formation and maintenance of myelin, but inhibits axon regeneration through its interactions with a sialoglycoprotien. c. OMGP (oligodendrocyte myelin glycoprotein)/arretin 3. Developmental axon repulsive cues (affect growth cone motility) a. Semaphorins – Sema4D expression is upregulated in the SC after injury. b. Slits c. Netrins d. Ephrins
Name a category of inhibitory molecules that blocks axon regeneration. Provide an example of a protein in that category.
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Mertens et al. show that in vitro using calcium imaging that neuronal networks from lithium responders reduce their activity in response to lithium chloride.
Give an example of relating in vivo symptoms to phenotypes seen in vitro with iPSC.
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[See PPT]
Describe inside-out and outside-in strategies to pack
newborn neurons. |
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[See PPT]
Describe how axoaxonic synapses reduce neurotransmitter release in the spinal cord?
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Fgf8 levels undergo graded increase rostrocaudally inducing specific Hox genes along the spinal cord.
What is the relationship between fgf8 signaling and Hox genes in the developing spinal cord?
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. Loss of intrinsic growth ability due to changes in gene expression following injury.
2. Persistence of extrinsic inhibitory molecules that block regeneration a. Neutralize inhibitory factors by: i. Inhibiting Nogo with antibodies or antagonists ii. Inhibiting Sema3A with small molecule inhibitors 3. Four approaches to promote regeneration: a. Promote intrinsic growth ability b. Provide a permissive environment: PNS nerve graft, neutralize inhibitory factors, modulate intracellular signaling. c. Provide an instructive environment: axon guidance cues. d. Cell replacement therapy
What are two factors that prevent axon regeneration following injury and four approaches to promote regeneration?
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What is
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What is
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presynaptic terminals: decrease neurotransmitter release
(local effect) Example: interneurons in the spinal cord presynaptic axon hillock: prevent the initiation and propagation of action potential (global effect) Example: Chandelier cells in V1
Compare the inhibition effects of axoaxonic synapses on presynaptic terminals and on presynaptic axon hillock.
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During early development, the hindbrain and the anterior portion of the spinal cord is transiently partitioned into transverse neuro-epithelial segments called rhombomeres. This lack of mixing is due to rhombomere specific expression patterns of Ephrin receptors (Eph) (also referred to as Eph kinase) and ephrins.
How is ephrin signaling important in the patterning of the hindbrain?
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1. Inhibitors of regeneration:
a. PTEN/mTOR pathway: PTEN (PTEN deletion promotes regeneration) b. PTEN/mTOR pathway: TSC1/2 c. GSK3b: inhibited by phosphorylation by Akt; deletion in RGCs enhances optic nerve regeneration. d. KLF4: knockdown of KL4 promotes optic nerve regeneration e. SOCS3: inhibits JAK-STAT signaling; knockdown promotes optic nerve regeneration 2. Promoters of regeneration: a. PTEN/mTOR pathway: activated Akt b. PTEN/mTOR pathway: activated Rheb c. PTEN/mTOR pathway: activated mTOR signaling d. c-Myc: overexpression enhances optic nerve regeneration.
List the signaling pathways or molecules that 1) inhibit regeneration and 2) promote regeneration.
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1. Generated iPS cells are “immature” in developmental age
2. Many specific cell types of interest do not have protocols yet to generate them.
Name 2 disadvantages of using hiPSC?
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EdU
Inducible Cre-LoxP system Non-replicating virus with markers
How do you determine what cell types a certain progenitor would give rise to at a certain developmental period?
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