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DPR: Lecture 7
Construction of Neural Circuits
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Video
http://libproxy.temple.edu/login?url=http://di
gital.films.com/PortalPlaylists.aspx?aid=1627&
xtid=41054
Section 7
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Stages of Brain Development
1. Cell birth (a.k.a. neural generation)
2. Cell migration
3. Cell differentiation4. Cell maturation
5. Synaptogenesis
6. Cell death/ synaptic pruning7. Myelogenesis (a.k.a. formation of myelin)
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Maturation: Axonal Growth
Axonal growth is similar to neural migration, in
that axons must travel great distances to
synapse onto their appropriate targets (think
about the nerves stretching to your big toe)
How can an axon possibly traverse such
complicated terrain to make the right
connections?
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Growth Cones
Growth Cones are dynamic ends of developingaxons that feel around for guiding factors totell it where to go
2 guiding factors:
Non-diffusible (e.g., Cell-adhesion moleculesor CAMs) act like velcro to pull the growth
cone along Diffusible (such as tropic molecules like Slit)
are chemical signals that either attract orrepel the growth cone
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Growth Cones
Lamellipodium
Lamellipodium =
sheet-like
expansion of axon
Filopodia form and
disappear; act as
feelers
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Growth Cone Video
http://www.youtube.com/watch?v=Fgmt2RBow
0I&feature=related
Why explore?
http://www.youtube.com/watch?v=Fgmt2RBow0I&feature=relatedhttp://www.youtube.com/watch?v=Fgmt2RBow0I&feature=relatedhttp://www.youtube.com/watch?v=Fgmt2RBow0I&feature=relatedhttp://www.youtube.com/watch?v=Fgmt2RBow0I&feature=related7/28/2019 Lecture 7 Neural Circuits(1)
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Cytoskeleton Microfilaments
Thread-like protein fibers
Mostly made of actin
Carry out cellular movements
Microtubules
Little tubes Made of tubulin
Scaffold for cell shape, alongwith tracks for movementshown in previous slide
Intermediate filaments Tensile strength
Neurofilaments are one type
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Red = Actin
Green =
Tyrosinated
microtubules
Blue = Acetylated
microtubules
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Protrusion = actin
moves forward
Engorgement =
microtubles invade,bringing organelles
along
Consolidation = actin
moves out, allowing
contraction
From Dent & Gertler, 2003
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Axon Guidance: 2 Flavors
Non-diffusible
Closely related (in space) to cells that distribute
them
Fine for short-range communication
Diffusible
More long-ranging
Can attractor repel
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Non-diffusible: Extracellular Matrix
Cell Adhesion Molecules
Fibronectin
Collagen
Laminin
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Non-diffusible: Calcium-independent
cell adhesion molecules (CAMs)
Homophilic:
ligands and
receptors
Bundle axons
together
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Non-Diffusible: Calcium-dependent
cell adhesion molecules (cadherins)
Also homophilic
More on these later
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Tropic signals
Guide axons to the correct location
Netrins = can be attractive or repellant
Slit (signal)/Robo (receptor) = repellant Semaphorins = repellant
Ephrin = forward and reverse signaling,
often repellant but can attract
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Calcium concentrations in netrin culture
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Topographic Maps
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Topographic Maps
How are they made?
Chemoaffinity hypothesis: specific neurons areguided to specific targets by specific recognitionmolecules
In the frog visual system, this is accomplishedwith ephrins
Remember, frog CNS can regenerate, unlikemammals!
Also, frogs eyes dont point forward, so there isan anteriorandposterioraspect to the retina
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In Chicks/Mice
Temporal retina -> anterior tectum
Plate anterior or posterior embryonic tectum
tissue, and grow retinal axons over it
Temporal axons prefer anterior tectum tissue!
Ephrins act as repellants,
Temporal axons with high levels of receptors can only
make it into anterior tectum with low levels of signal Nasal axons with low levels of receptor can make it
into areas even with high levels of signal
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Tolerance to repellant
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Synaptogenesis
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Synaptogenesis
1. Initiation: local recognition via cadherins
2. Induction: More adhesion, cytoskeleton
recruitment, proper protein recruitment
1. Postsynaptic density = localization of
neurotransmitter receptors & other proteins
2. Neurexin -> presynaptic membrane
3. Neuroligin -> postsynaptic membrane
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Trophic Interactions
Tropic = axon guidance
Trophic= nourishment -> regulates growth
and survival of surrounding cells
Apoptosis = programmed cell death
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Competitive Interactions in Synapse
Formation
Lots of overlap to start
Those that fire together, wire together
Only the strong survive
When an input appropriately innervates atarget, inputs and targets fire at the same time& synapses are strengthened
When an input does not appropriatelyinnervate a target, it eventually loses the
competition and retracts
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Neurotrophins
Nerve growth factor (NGF)
Brain-derived neurotrophic factor (BDNF)
Neurotrophin-3 (NT-3)
Neurotrophin 4/5 (NT-4/5)
These are important for supporting the
outgrowth of neurites and survivalof neuronsgenerally
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Chick sensory ganglion: No NGF Chick sensory ganglion: With NGF
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Normal superior cervical ganglion
Anti-NGF serum
NGF has local effects on neurites but
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NGF has local effects on neurites, but
global effects on neural survival
Neurotrophin receptors have tyrosine
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Neurotrophin receptors have tyrosine
kinase domains
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