Lecture 7 Neural Circuits(1)

7/28/2019 Lecture 7 Neural Circuits(1)

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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=related


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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

Lecture 7 Neural Circuits(1)

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