Exam II Practice Questions Flashcards
The downstream target of many of the growth and guidance signaling molecules is
a. Integrins
b. Actin and cytoskeletal elements
c. Extracellular matrix
d. Immunoglobulins
Actin and cytoskeletal elements
Dendritic spines are
a.Static structures that never change
b.Structures that are plastic in development but static in adulthood
c.Structures that maintain some level of plasticity into adulthood
d.Always transient structures that never stabilize
Structures that maintain some level of plasticity into adulthood
Initiation of postsynaptic assembly is largely initiated and organized by the recruitment of
a. AMPA receptors
b. NMDA receptors
c. PSD-95
d. Stargazin
PSD-95
Which of the following signal molecules operating post-synaptically is responsible for forming an inhibitor synapse?
a. Wnt 7a
b. Wnt 5a
c. Wnt 5a and 7a together
d. Wnt-er is coming
Wnt 5a
GEFs activate small g proteins by
a. Phosphorylating the associated GDP
b. Dephosphorylating the associated GTP
c. Exchanging GDP to GTP
d. Hydrolyzing ATP
Exchanging GDP to GTP
Neurotransmitter release in response to an action potential depends on
a. Sodium channel closing
b.Sodium influx in the terminal bouton
c.Calcium influx in the terminal bouton
d.Potassium efflux from the terminal bouton
Calcium influx in the terminal bouton
What behavior was used by Kandel to study habituation
a. Siphon withdrawal reflex
b.Tail withdrawal reflex
c.Gill withdrawal reflex
d.Inking reflex
Gill withdrawal reflex
In habituation, repeated harmless stimulation leads to
a.Increased responding
b.Decreased responding
c.No change in responding
Decreased responding
- Calcium influx in response to action potential results from
a.Vesicle fusion
b.NT release
c.Voltage-gated calcium channel opening
d.Voltage-independent calcium channel closing
c.Voltage-gated calcium channel opening
- Activation of PKC by the Gq pathway requires
a.Activation of adenylyl cyclase
b.Activation of phospholipase C
c.Binding glutamate
d.Action potential broadening
b. Activation of phospholipase C
- The open-book experiment demonstrates
a.The axon’s attraction to Netrin
b.The axon’s attraction to Slits
c.The axon’s attraction to the floor plate
d.The axons change from attraction to the floor plate to not being attracted to the floor plate
d. The axons change from attraction to the floor plate to not being attracted to the floor plate
- What receptor mediates the change in axon guidance in commissural axons
a. ROBO
b. DCC
c. Eph
d. Slit
a.ROBO
Which is a receptor for Slits?
a. ROBO
b. DCC
c. Unc-5
d. Netrin
a.ROBO
Before reaching the floor plate, netrin binds which receptor?
a. ROBO
b. DCC
c. Unc-5
d. Slit
b.DCC
What does Netrin bind after reaching the floor plate?
a. ROBO
b. DCC
c. Unc-5
d. Both b and c
d. both b and c
The downstream target of many of the growth and guidance signaling molecules is
a. Integrins
b. Actin and cytoskeletal elements
c. Extracellular matric
d. Immunoglobulins
b. actin and cytoskeletal elements
Wnts
a.Have many diverse functions in development
b.Are a class of signaling molecules
c.Appear to have functions both in the background as well as in adulthood
d.All the above
d. all the above
Neurotransmitter release in response to an action potential depends on
a.Sodium channel closing
b.Sodium influx in the terminal bouton
c.Calcium influx in the terminal bouton
d.Potassium efflux from the terminal bouton
Calcium influx in the terminal bouton
There are two basic zones in the terminal bouton about the population of vesicles as defined by Bailey and Chen (1988) they are:
a.The storage pool and the readily releasable pool
b.The storage pool and the inactive zone
c.The docked and releasable zone
d.Fused and total vesicle population
The storage pool and the readily releasable pool
Calcium influx in response to action potential results from
a.Vesicle fusion
b.NT release
c.Voltage-gated calcium channel opening
d.Voltage-independent calcium channel closing
Voltage-gated calcium channel opening
Which of the following is a calcium sensor is involved in exocytosis?
a.Synaptobrevin
b.Synaptogamin
c.Syntatopyshin
d.Synaptosynaptic
Synaptogamin
The open-book experiment demonstrates
a.The axon’s attraction to Netrin
b.The axon’s attraction Slits
c.The axon’s attraction to the floor plate
d.The axons change from attraction to the floor plate to not being attracted to the floor plate
The axons change from attraction to the floor plate to not being attracted to the floor plate
What receptor mediates the change in axon guidance in commissural axons
a.ROBO
b.DCC
c.Eph
d.Slit
ROBO
Which is a receptor for Slits?
a. ROBO
b. DCC
c. Unc-5
d. Netrin
ROBO
Before reaching the floor plate, netrin binds which receptor?
a. ROBO
b. DCC
c. Unc-5
d. Slit
DCC
What does Netrin bind after reaching to floor plate?
a. ROBO
b. DCC
c. Unc-5
d. Both b and c
D. both b and c
Which of the following is a small g-protein involved in mediating netrin’s attractive signal?
a.Unc-5
b.Nogo Rhota
c.CDC 42
d.Robo
Unc-5
Which of the following receptors is not present in the membrane upon approach to the midline?
a.ROBO
b.DCC
c.Unc-5
d.Slit
ROBO
Vertebrate cells are called:
a.Astroglia
b.Microglia
c.Radial glia
d.Neural precursors
Neural precursors
Which of the following is the best example of scaffold-dependent migration?
a.Rostral migratory stream
b.Radial migration
c.Tangential migration
d.Neural crest migration
Radial migration
What ion is the most responsible neurotransmitter release?
a. Sodium
b. Potassium
c. Calcium
d. Chloride
Calcium
Which ion when a selective ion channel is opened for it, will flow out of the cell?
a. Sodium
b. Potassium
c. Calcium
d. Chloride
Potassium
Which ion when a selective ion channel is opened for it, will flow against its electrical gradient?
a. Sodium
b. Potassium
c. Calcium
d. All of the above
e. None of the above
Potassium
Which ion when a selective ion channel is opened for it, will flow along its chemical gradient?
a. Sodium
b. Potassium
c. Chloride
d. All of the above
e. None of the above
Sodium
In which direction does sodium flow when the electrical gradient is manipulated so that it matches the concentration gradient exactly?
a. Into the cell
b. Out of the cell
c. No net flow
No net flow
Identify the four phases of axon growth
- encounter substrate: substrate approaches signal
- Protrusion: filopodia and lamellopodia extend from growth cone
- Engorgement: filopodia and lamellopodia in actin framework to extend further into growth cone
- Consolidation: the final step where filopodia begins exploration of the environment
Early signaling is dependent or independnet of gene expression. How do we know?
Independent because Wnt signaling is local. Blocking ribosomes doesn’t inflict any change.
Identify and briefly describe three of six basic mechanisms of axon guidance
- Extracellular matrix adhesion: growth-promoting molecules in the extracellular matrix
- Cell surface adhesion: cell surface molecules on neural cell
- Fasciculation: a growing axon encounters another axon from a “pioneer” neuron and tracks along it
Wnts are important to synaptogenesis in development; do they play a role in synaptic maintenece/loss in adults? How do we know?
- Synaptogenic factors are ideally suited to modulate synaptic stability. Indeed, Wnt signaling has now been demonstrated to regulate synaptic maintenance in mature neurons.
- Dkk1 rapidly induces the delocalization of pre and postsynaptic components in mature and stable hippocampal synapses.
- This effect is accompanied by a reduced number of SV recycling sites These findings provide evidence that endogenous Wnt signaling is required for synaptic maintenance nerative diseases
Regarding the open-book experiment studying commissural axon growth, we have placed an ectopic floor plate on the far side of the endogenous floor plate. The axon has grown across the midline and has ignored the ectopic floor plate. What can we conclude from this, and what does it rule out?
The observation that the axon has grown across the midline and ignored the ectopic floor plate suggests that the axon’s response to guidance cues is not solely determined by the presence of the floor plate itself but rather by a graded distribution of attractive and repulsive cues. This finding implies that other guidance cues, likely diffusible factors or substrate-bound molecules, play a dominant role in guiding commissural axon growth. It rules out a simplistic model where the presence of any floor plate, regardless of its location, would attract axons. Furthermore, it suggests that axon guidance is a nuanced process involving the integration of multiple signals and their spatial gradients, highlighting the complexity of neural circuit formation.
Describe the activation/deactivation process of small g proteins
Activation:
- Ligand binding to cell surface receptors triggers GDP/GTP exchange factor (GEF) activation.
- GEFs catalyze the exchange of GDP bound to the small G protein with GTP.
- GTP binding induces a conformational change in the small G protein, leading to its activation
Deactivation:
- GTPase-activating proteins (GAPs) facilitate the hydrolysis of GTP to GDP.
- This hydrolysis reduces the affinity of the small G protein for its effectors, leading to deactivation.
- The GDP-bound form of the small G protein has a lower affinity for effector proteins and returns to its inactive state until the next activation cycle
What seems to be the most important factor for the selection of the neurite to become the axon? Describe some evidence for this
-Neurite outgrowth: the neurite that is the longest becomes the axon
-Evidence: severing
-If the longest projection is cut shorter, it will not become the axon
-Neurite stains as tau before severing
Describe the role that motor proteins play in the extension of the axon
- Generate tension and move raw materials up and down the axon
- The movement of cargo causes MT near the growth cone to be pushed, being captured by filopodia
Describe the growth cone. Describe how its structure mediates its dynamics. Include its zones, their structures, and their dynamics
-The growth cone is the site of axonal growth
-Lamellipodia: sheet
-Filopodia: fingers
-Actin is responsible for growth cone dynamics
-Growth cone zones: Peripheral (P) domain, Central (C) domain, Transition (T) zone
Open Book Experiment
-An open book culture is made by cutting along the dorsal edge of the neural tube and opening it up. The tissue is then laid flat with the floor plate in the middle.
-Axons grow towards the floor plate and cross over to the other side.
-If an extra piece of floor plate is placed beside the explant, on the same side as the labelled axons, they head towards to ectopic floor plate attracted by the netrin that it produces.
-However, if the extra floor plate is placed on the other side of the explant, such that the commissural growth cones have already crossed over the floor plate before becoming exposed to netrin produced by the ectopic floor plate tissue, they are no longer attracted to it.
-If floor plate tissue is excised from the explant, commissural axons are now attracted to the extra floor plate tissue.
Describe the signaling process involved in commissural axon guidance. Be as complete as possible
Commissural axons are able to cross the midline as a result of losing sensitivity to the midline attractant netrin.
Slit encodes a secreted protein that is expressed by the midline glia and acts as a chemorepellent signal. An important role for Slit at the ventral midline is to repel commissural axons from the midline once they have crossed it.
The ROBO genes encode receptors for Slit, so axons in ROBO mutant flies are unable to respond normally to Slit’s chemorepellent activity.
Commissural axons are insensitive to Slit’s chemorepellent activity before crossing but they become sensitive to it after they have crossed.
apart of the open book experiment mechanism
Receptor interactions of the open book experiment
In growth cones that express both ROBO and DCC, binding of Slit to ROBO is thought to block the activity of DCC. This may account for the finding that commissural axons lose their sensitivity to netrin upon reaching the midline. After crossing the midline, DCC expression is down-regulated so axons remain insensitive to netrin
Describe the canonical Wnt pathway
- Wnt proteins bind to cell-surface receptors of Frizzled family, activating intracellular Disheveled
- Activated Disheveled inhibits axin/GSK3B/APC complex
- In absence of Wnt, the axin/GSK3B/APC complex causes phosphorylation of B-catenin, causing B-catenin to degrade
- Inhibition of complex allows B-catenin to enter the nucleus and displace a repressor protein, and in combo with TCF/CEF family, affect transcription
-Frizzled activation blocks GSK3B phosphorylation of MAP1B, allowing it to associate with MTs, leading to looping
Describe the wnt pathway in early synaptogenesis and its consequences on the growth cone and axon as it begins to form the presynaptic complex
- Wnt causes dramatic remodeling of the growth cone
- GSK3B phosphorylates MAP1B, which prevents MAP1B association with MTs → prevents loops, maintains dynamics(canonical)
- Wnt blocks GSK3B to prevent MAP1B phosphorylation, allowing it to associate with MTs, leading to looping, loss of APC from MT + ends, and capture of synapse associated proteins
Describe the wnt pathway in early synaptogenesis and its consequences on the postsynaptic side
- In postsynaptic dendrites, Wnt7a promotes spine morphogenesis, PSD-95 recruitment, and synaptic strength by signaling via Dvl1 and CAMKII
- Wnt5a signals postsynaptically to promote PSD-95 clustering via excitatory JNK activation, and GABAA receptor clustering via inhibitory CAMKII
- When presynapse begins to release Wnt to the postsynapse:
*Wnt7a induces more prominent formation of dendritic spines
*PSD-95 protein recruitment, which is a MAGUK or scaffolding protein that holds synapse in place
Repeately stimulating the siphon in a benign manner will lead to what form of learning?
- Touching the siphon leads to the gill-withdrawal reflex; repeated stimulation leads to a progressive depression of synaptic transmission between the sensory and motor neurons, seen as a decrease in size of the motor neuron EPSP with no change in the action potential in the presynaptic sensory neuron; decrease in gill withdrawal (habituation)
- The amount of glutamate released from presynaptic terminals of sensory neurons decreases
- Fewer synaptic vesicles are released with each AP in the sensory neuron
- The sensitivity of the postsynaptic glutamate receptors does not change
Binomial Distribution
What does the n value determine?
number of vesicles releasing in response to an AP
Binomial Distribution
What does the p value represent?
Probability of any individual vesicle releasing NT in response to an AP (action potential)
Binomial Distribution
What is the binomial distribution equation?
Binomial Distribution
What does the x variable represent?
the number of vesicles releasing in response to an AP
Mechanism of Gs activation
- Epinephrine binds to the receptor
- Dissociation of G-protein from the receptor
- GDP exchanged for GTP → activates the α subunit
- α subunit dissociates from other subunits of the G-protein
- α subunit binds to adenylyl cyclase (effector protein)
- Adenylyl cyclase is stimulated → converts ATP to cAMP
- cAMP → PKA
- Catalytic subunit of PKA dissociates from regulatory subunit and goes on to phosphorylate proteins within the cells → cascade of events
Mechanism of deactivation of Gs pathway
- GTP is hydrolyzed to GDP
- Inactivation of α subunit → α subunit dissociates from adenylyl cyclase
- Reassociates with beta/gamma subunit
- Adenylyl cyclase deactivates
- Phosphodiesterase destroys remaining cAMP
- Regulatory unit of PKA reassociates with the catalytic unit
- No more phosphorylation of proteins
- Protein phosphatase dephosphorylates proteins
Describe the mechanism that underlies classical conditioning
-Calcium enters presynaptic terminal in response to AP
-Calmodulin binds this Ca2+ and this associates with adenylyl cyclase
-This facilitates adenylyl cyclase activity, makes ready for an exaggerated response to 5HT activation
-Adenylyl cyclase acts as a coincidence detector here
-Postsynaptic mechanism at play here as well, also dependent on Ca2+ influx
-NMDA receptors mediate rapid changes associated with synapse strengthening
-Also leads to production of retrograde signal to coordinate with presynaptic terminal
Peripheral (P) domain
-Actin filaments (F-actin bundles) form filopodia and lamellipodia
-Dynamic MTs explore the region
Central (C) domain
Encloses stable, bundled MTs that enter the growth cone from the axon shaft, in addition to numerous organelles, vesicles and central actin bundles
Transition (T) zone
-Sits at the interface between the P and C domains
-Actomyosin contractile structures (actin arcs) lie perpendicular to F-actin bundles and form a hemicircumferential ring
The six basic mechanisms for axon guidance
- Extracellular matrix adhesion
- Cell surface adhesion
- Fasciculation
- Chemoattraction
- Contact inhibition
- Chemorepulsion
Delta Notch
Describe the process of SOP commitment
- The Drosophila PNS is formed by sense organ precursors (SOPs)
- In this system, the ectodermal cells have neural competence, but only a small portion become committed to neural fates
- Proneural genes are absolutely required for neural commitment; they encode transcrip. factors that have the bHLH domain
- Proneural genes are originally expressed in proneural clusters- only these cells have neural competence
- Within a cluster, only one cell makes it to commitment
- The committed cell expresses the Notch ligand, Delta, where it contacts Notch receptors on the surrounding cells of the proneural cluster
- Notch reception results in inhibition of neural commitment
Fasciculation
a growing axon encounters another axon from a “pioneer” neuron and tracks along it
Cell surface adhesion
cell surface molecules on neural cell
Extracellular matrix adhesion
growth-promoting molecules in the extracellular matrix
