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Block 5; Week 4 > Plasticity-vonBartheld > Flashcards

Flashcards in Plasticity-vonBartheld Deck (85):

What is a growth cone?

extension of a developing neuron
this is actin-supported growth
they are dynamic & react to the environment, go where the axons want to.


What are filipodia?

these are extensions of the growth cone


What does it mean that the growth cones are actin-supported?

it means that globular actin is assembled into F-actin that extend into the growth cone. This building is a calcium dependent process.
Tubular binding proteins are involved.


If the growth cones encounter repulsive clues what do they do?

they break down the F-actin & disassemble things.


What do growth cones do at decision points?

they are at a cross roads. and they decide what they will do...make change directions. then they commit.


What are some non-diffusible signals for axon guidance on cell surfaces?

types of cell adhesion molecules:


What are some non-diffusible signals for axon guidance on extracellular matrix?

**these are all types of integrins


What are some important diffusible signals for axon guidance?

ephrins--retinotectal map gradients
semaphorins-chemorepellent, anchored to cell surfaces


T/F Adhesion molecules, such as laminin, fibronectin, integrin, CAMs & cytoplasmic signaling molecules are important in growth cone growth.



When does a growth cone collapse?

when it doesn't like its environment


What is chemotropism?

this is what chemically guides growth cones. Chemoattractants v. Chemorepulsion.


Which types of axons grow in the anterior & posterior tectums?

temporal axons only grow anteriorly.
nasal axons grow both anteriorly & posteriorly


What is the neurotrophic hypothesis?

target cells release trophic molecules that connect with synapse of neurons & are transported to the neuronal body via retrograde transport
**there is a competition b/w neurons for these trophic cells.


What % of neurons die?

40-50% of neurons die b/c of competition for trophic molecules
**if they don't get trophic molecules--get programmed cell death


What is the proper way to do cell counting?

via 3D counting not profile counting


What did Rita Levi discover?

she also took this everyday until she died at 103.


What are the key functions of neurotrophins?

synaptic plasticity


What happens to the pheochromocytoma cells found in the adrenal medulla when they are exposed to NGF?

they start to look like neurons! The PC12 cells differentiate.


What are the different types of neurotrophin receptors?

Trk A, B, C (tyrosine kinase) receptors & p75 receptor.


Which neurotrophins bind to Trk A?



Which neurotrophins bind to Trk B?

BDNF (brain derived neurotrophic factor)*structurally similar to NGF
NT3 (with less affinity)


Which neurotrophins bind to Trk C?

NT3 (with greater affinity)


Which neurotrophins bind to p75?

all of the neurotrophic factors bind to this receptor with equal affinity


We know that trophins are important in development & plasticity. What are the different families of trophic factors?

NGF-like factors (neurotrophins)
GDNF-like factors
FGF family (fibroblast growth factor)
IGF (insulin like growth factor)


Describe the signaling endosome.

this starts off as a vesicle in the target cell. It contains the trophic factor. It pinches off of the cell as a signaling endosome that has a receptor for multiple things.
It travels along microtubules towards the neuron's cell body. It attaches to dynein.


If the endosome were not traveling in the direction toward the cell body, which molecule would it attach to instead of dynein?

kinesin. anterograde direction.


What are htt & HAP?

htt: Huntingtin
HAP: huntington associated protein
this complex is attached to the signaling endosome & is responsible for transporting the trophic factor to the cell body as a part of the molecular motor.


How could a mutation in htt be related to Huntington's disease?

htt mutation
transportation of the trophic factor not as efficient
striatum doesn't receive enough BDNF
Too few neurons releasing ACh & such.
hyperkinetic syndrome (Huntington's)
*possible therapy: BDNF administration to patients


Describe the effect of knocking out a signal trophic factor on the PNS & CNS.

PNS: huge effect b/c usu one afferent to one target with one neurotrophin
CNS: less of an impact b/c redundancy present. Multiple afferents & multiple targets. Multiple trophic factors at work.


T/F Functionally distinct DRG neurons respond to different trophic factors.



Which trophic factor do nerve endings respond to? The 3 types that respond to pain.

respond to NGF


Which trophic factors do the muscle spindle respond to?



Which trophic factors does the pressure-sensitive Merkel disc respond to?



Which trophic factors does a hair follicle respond to?



BDNF induces which kind of growth?

dendritic growth


Dr. Von B made a point about pyramidal cells in different layers of the cortex having different structures to their dendrites. How was this made possible?

Regulated by the trophic factors present there. Dependent on the afferent fibers going there.
**Remember that neurotrophins shape the morphology of neurons.


In general, if your trophic factors bind more to the Trk receptors than the p75 receptor...what will be the result?

Cell survival.


In general, if your trophic factors bind more to p75 than Trk receptors, what will be the result?

Cell death via apoptosis.


The Trk receptors are connected to 3 pathways that ultimately alter________.

gene transcription.


So...Dr. Von B emphasizes that this is simplified. BUt...what are the 3 pathways of the Trk receptor?

1. PI3 Kinase
2. ras (includes MAP kinase)
3. PLC (ends up releasing Ca++ & activating PKC)


What is the result of the Trk receptor PI3 kinase pathway, generally speaking?

cell survival


What is the result of the Trk receptor ras pathway, generally speaking?

neurite outgrowth
neuronal differentiation


Which type of receptor binds pro trophic factors with higher affinity? What is the significance of this?

p75 receptor binds pro trophic factors with higher affinity.
so...if you cleave EVERYTHING then you will probably get cell survival.


What is the result of the Trk receptor PLC pathway, generally speaking?

activity-dependent plasticity


So...Von B said this is simplified...but what are the possible outcomes of the p75 receptor activation?



What is the result of p75 SC1 pathway?

cell cycle arrest


What is the result of the p75 NADE pathway?

cell death


What is the result of the p75 RhoA pathway?

neurite growth (finally some good news!!)


What's the deal with polyneural innervation?

at the beginning of an organism's muscle fiber has multiple innervations. One ganglion cell has multiple innervating fibers.


How is polyneural innervation eliminated? adults one muscle fiber-one innervating fiber.
One ganglion cell-one innervating fiber.
The neurons that innervate a muscle fiber, for example, compete for trophic factors. Whichever one wins...remains. The rest are eliminated.


What did von B emphasize about the study of the neuromuscular jcns in chick eye muscles?

He emphasized that this study shows that originally multiple neuronal fibers were innervating one endplate. But then, after competition & age...only one fiber innervates each endplate.


What is a critical period for development? What are examples of things that this applies to?

there is a special time period during which the environment influences formations of neural circuits.
This especially applies to visual development--ex w/ ocular dominance columns & binocular vision.
**also applies to olfactory development
language development
emotional processing development
other sensory & motor development


Describe the transneuronal transport used to make the critical period experiments work.

Radioactively labeled AA injected into one retina. This is taken up by retinal ganglion cells & incorporated into proteins that are put into neurons & transported anterograde to the LGN of the thalamus. LGN neurons take it up & transport it to the cortex (also via anterograde axonal transport). In the cortex about half the terminals are labeled.


What's special about layer 4 of the brain?

So...this is the layer right underneath the cortex (1-3). Here, there is not yet segregation b/w the right & left eyes. They don't come together until you get to the cortex.
The radioactively labeled AA looks like light bands in this region (ocular dominance columns).


Describe the development of ocular dominance columns of a cat at 2 wks, 3 wks, 6 wks, 13 weeks?

2 weeks: overlap
3 weeks: still some overlap
6 weeks: columns visible, some overlap still
13 weeks: complete segregation & formation of columns


T/F Light deprivation of an eye during the critical period reduces layer IV input & reduces the size of that eye's ocular dominance columns.

Completely true.


Describe the effects of monocular deprivation in a kitten (compare this to normal data of a cat).

Normal: bell-curved distribution of data showing that on one half of the brain you get info from both eyes. Binocular vision.
Monocular Deprivation of Kitten (during critical period):
only get info from ipsilateral eye to the cortex.


Describe the effects of monocular deprivation in an adult cat (compare this to other data).

Cat: bell-curved distribution (maybe some consequences) but mainly fine. Still get binocular vision once you let the cat see.
Kitten: only ipsilateral eye.
Normal: looks similar to cat. Info from both eyes goes to both sides of cortex. Binocular vision.


Describe the different results of monocular deprivation of a kitten during the critical period for 3 days v. 6 days.

3 days: start to lose the contralateral eye.
6 days: only have ipsilateral.
Takeaway: without visual experience, not wired for input from both eyes on both sides of the brain.


Describe the strabismus study.

Cut a nerve in the kitten to make it strabismic. AFter living like this, don't have the neuronal capability of taking input from both eyes & making binocular vision.


Explain how the TTX asynchronous stimulation experiment yielded similar results to the strabismus study.

So...this study silenced the input coming into the eyes via TTX. They then put electrodes in the optic nerves.
**In one half of the study, they synchronously stimulated the 2 nerves.
-Results: normal ocular dominance columns
(could receive input from both eyes)
capable of binocular vision.
**In another half of the study, they asynchronously stimulated the 2 nerves.
-Results: ocular dominance columns could NOT receive input from both eyes.
Binocular vision was not possible.
similar results to the strabismus study.
**Takeaway: the pattern of activity matters!


How can some species develop ocular dominance columns & segregation in utero?!

Even tho they can't see anything...there are retinal waves of correlated activity.
Even w/o sight-->segregation & ocular dominance columns already start to form!
Lucky little guys.


What does Hebb's postulate say?

Neurons that fire together wire together.
If there is a set of neurons that fire together & do so successfully-they will form more synapses & survive. The neurons that asynchronously fire & not very well--lose their synapses. They don't die--just move on to something else.
Happens w/ layer IV input.


Why is it so important to treat a child's strabismus as soon as possible? How do cat studies support this?

it is important b/c if they pass out of the critical period they will never be capable of binocular vision.
Cat studies: critical period of about 1 week. Past that time frame--opened closed eye & didn't regain vision.


Aside from cats & sight...what are some other examples of critical periods?

Konrad Lorenz discovered a critical period for ducks. After birth for a period of time they imprint on the first thing they see as their mother.


T/F The mature brain is entirely hard wired.

False. THere is some plasticity that extends into adulthood.


Describe what short term plasticity looks like.

So...maybe you have multiple AP firings in a row. You get a buildup of calcium in the cell for the release of NT. Once you stop firing, you will have a higher post-synaptic membrane potential & easier release of NT b/c the calcium can't get out of the cell fast enough. Will eventually be reduced...
Also get a post-tetanic potentiation spike in short term plasticity.


What is habituation?

a decrease in response to a benign stimulus when that stimulus is presented repeatedly
*fewer NT vesicles are transported to the active zone


What is sensitization?

an enhanced response to a wide variety of stimuli after the presentation of an intense or noxious stimulus
***can be short term or long term
**like Pavlov!


What types of substances are involved in making short term sensitization happen?

second messengers
ion channels


What types of substances are involved in making long term sensitization happen?

changes in gene expression
protein synthesis (PKA & MAPK)
an increase in the number of synapses


Describe what they found in their experiment with snail sensitization in the gill withdrawal reflex.

Touched the skin & shocked the tail of the snail. This input went thru interneurons to get to the motor neuron. The addition of the tail shock enhanced the release of NT to the motor neuron (sensitization). ON a small scale the interneuron caused activation of a G protein on the main sensory neuron of the reflex. cAMP increased. PKA activated. K+ & Ca++ channels opened. More vesicles with NT released on motor neuron. Enhanced response.


The hippocampus is a model for plasticity...describe the set up of its neurons.

CA3 pyramidal cell-->Schaffer collateral-->CA1 pyramidal cell
Used in long term potentiation studies.


What are 2 ways to get long term potentiation in the hippocampus study?

1. high frequency stimulation-get higher amplitude after tetanus
2. paired pulses


T/F In order for paired pulses to cause long term potentiation they have to be temporally related.

True. Have to happen at roughly the same time or no effect.


How does magnesium relate to long term potentiation?

AMPA receptors are open, but NMDA receptors on the motor neurons are blocked by Mg++. It takes a lot of NT force release to get rid of the magnesium & allow for Na+ influx thru the NMDA receptor. This addition of the NMDA receptor then causes long term potentiation.


What are retrograde effects of long term potentiation? What are some possible mediators of this?

Something (maybe NO or BDNF) comes back from the motor neuron that has undergone LTP & causes the recruitment of more NT vesicles to be released from the sensory neuron.


T/F Motor neurons that want LTP to continue can also add more NMDA receptors to their terminals.

False. AMPA receptors--otherwise true.


If you want long-lasting LTP...which guys do you get on your team?

involves CREB
get transcription of more proteins & synapse growth molecules


Give an example of long term depression in the cerebellum.

When the purkinje cells are coincidentally fired by climbing fibers & parallel fibers...the synapse internalizes AMPA receptors & reduces the strength of activation.
jUst one example of long term depression.


T/F Kinases are usu involved in LTP.

Kinases--LTP True!!!


T/F Kinases are usu involved in LTD.

False. PHosphatases are involved in LTD. They're mean & taking away a phosphate...they're depressed & want everyone else to be too.


T/F Maintenance of LTP requires protein synthesis.



What is the relationship b/w epilepsy & LTP?

it is thought that maybe epilepsy is caused by too many factor that set up the patient's neurons for LTP


Give 2 examples of plasticity in the adult cortex.

1. lose a finger...that area of the cortex that was reserved for that finger gets taken over by the surrounding fingers (either by sprouting or lack of stimulation)
2. train certain fingers---take up more area in the cortex.