Quiz 2 Preparation

Question 1

T/F: The neurotransmitter that a neuron releases is not always fixed.

Answer 1

True

Question 2

What determines the neurotransmitter that the neuron releases?

Answer 2

transcription factor programs– otherwise neuron will default to it’s hardwired fate

Question 3

What can change neurotransmitter identity once the neurotransmitter is determined by TFP’s?

Answer 3

experience and target innervation

Question 4

Neurotransmitter identity is plastic

Answer 4

Changes through rewiring and connectivity

Question 5

Is a neuron’s neurotransmitter phenotype fixed or flexible?

Answer 5

It is hardwired but can change based on experience and target derived signals

Question 6

T/F: Sympathetic neurons are initially specified with a
Noradrenergic transmitter phenotype (start with a noradrenergic fate). Most of these neurons will retain this transmitter phenotype.

Answer 6

True

Question 7

For Neural crest differentiation, what are the first and second this that give rise to sensory neurons?

Answer 7

1) Ngn2 + FoxS1 = sensory precursor
2) Ngn1 = sensory neuron

Question 8

What transcription factors turn a sensory neuron into nociceptive neuron?

Answer 8

Runx1 and TrkA

Question 9

What transcription factors turn a sensory neuron into proprioceptive neuron?

Answer 9

Runx3 and TrkC

Question 10

How do neural crest cells differentiate?

Answer 10

They give rise to sympathetic and sensory neurons. Sensory neurons are fixed, while sympathetic neurons can change their fate.

Question 11

If a gland secretes IL-6 cytokine, it transforms a ______ neurons fate to _______ (instead of noradrenergic)

Answer 11

1) sympathetic
2) cholinergic

Question 12

How do peripheral targets influence neuronal fate?

Answer 12

Secreted signals like IL-6 can change neurotransmitter phenotype, especially in sympathetic neurons.

Question 13

T/F: In CNS, neurotransmitter phenotype is less fixed compared to the periphery.

Answer 13

FALSE– more fixed

Question 14

bHLH? (transcription factors)

Answer 14

Basic Helix-Loop-Helix

Question 15

What are examples of bHLH?

Answer 15

Neurogenin and Mash1

Question 16

bHLH TF are expressed in what cells?

Answer 16

neuroepithelial cells (not in mature neurons)

Question 17

What does it mean for these TFs to be expressed in neuroepithelial cells?

Answer 17

CNS neurotransmitter identity is largely determined before differentiation, migration, and final specification.

Question 18

Is neurotransmitter phenotype in the CNS is flexible like in the periphery

Answer 18

No, CNS neurotransmitter identity is more “hardwired” due to early transcription factor expression before differentiation.

Question 19

Neurogenin 1 and 2 give rise to what neuroepithelial cells in the cerebral cortex?

Answer 19

dorsal

Question 20

Mash1 give rise to what neuroepithelial cells in the cerebral cortex?

Answer 20

ventral

Question 21

What is the concept of apoptosis?

Answer 21

When over half of all neurons born during development die due to programmed cell death

Question 22

Why does apoptosis occur?

Answer 22

The brain overproduces neurons, and only those that establish proper connections survive.

Question 23

What does apoptosis ensure with this process?

Answer 23

This ensures efficiency: neurons must compete for survival signals, eliminating excess cells that don’t form proper connections.

Question 24

Why do so many neurons die during development

Answer 24

Neurons are overproduced, and competition for survival factors determines which ones live. This ensures efficiency and proper wiring.

Question 24

T/F: Motor neurons (MNs) depend on muscle targets for survival.

Answer 24

True

Question 25

When adding an extra limb bud to a chick embryo, the area that received the additional limb bud from transplantation exhibited less neuronal death than the control side! What does this mean and what does this prove?

Answer 25

Adding an extra limb bud to a chick embryo → More motor neurons survive. Removing a limb bud → More motor neurons die. Trophic signals from muscles prevent motor neuron death.

Question 26

How do muscle targets influence motor neuron survival?

Answer 26

Muscle-derived signals provide essential survival factors. More muscle tissue = more motor neuron survival.

Question 27

What does blocking muscle activity do?

Answer 27

Increases MN survivalW

Question 28

What is Curare and what does it prevent?

Answer 28

- a drug that blocks acetylcholine receptors in muscles - prevents normal synaptic activity → rescues many neurons from dying

Question 29

T/F: Synaptic activity normally triggers localized release of a pro-death signal from muscle, which kills about 25% of motor neurons.

Answer 29

True

Question 30

How does synaptic activity affects motor neuron survival?

Answer 30

Active muscles release signals that contribute to MN death. Blocking muscle activity (e.g., with curare) rescues more MNs.

Question 31

What are the three major neurotrophins?

Answer 31

NGF (Nerve Growth Factor) BDNF (Brain-Derived Neurotrophic Factor) NT-3 (Neurotrophin-3)

Question 32

What is the neurotrophic factor hypothesis?

Answer 32

Neurons must compete for survival factors

Question 33

What are neurotrophins?

Answer 33

Small proteins secreted by target tissues that prevent apoptosis in neurons.

Question 34

Key Experiment!!

Answer 34

Injecting NGF into an embryo → More neurons survive. Blocking NGF → More neurons die. This confirms that NGF is a critical survival signal.

Question 35

Why do neurons die despite being "healthy"?

Answer 35

They lack enough neurotrophic factors, leading to apoptosis.

Question 36

Two Main Neurotrophin Receptors

Answer 36

Trk Receptors → Promote survival. p75 Receptor → Promotes cell death (binds all neurotrophins with low affinity).

Question 37

Survival depends on receptor activation"

Answer 37

If Trk is activated, neurons live. If p75 is activated, neurons die.

Question 38

How do neurotrophins influence survival?

Answer 38

Neurotrophins bind Trk receptors for survival, but if they bind p75 receptors, neurons undergo apoptosis.

Question 39

What is the binding of NGF to TrkA activates survival pathways?

Answer 39

FRS2 → Ras Pathway → Promotes differentiation. PI3-K Pathway → Promotes survival.

Question 40

What are the Cell Death (Apoptosis) Pathways?

Answer 40

Extrinsic Pathway: Activation of death receptors on the cell surface. Intrinsic Pathway: Mitochondria release signals to activate caspases, leading to apoptosis.

Question 41

What are caspases?

Answer 41

Key executioners. Caspase-9 (initiator) is inhibited by PI3-K. Caspase-3 (executioner) completes cell death.

Question 42

How does NGF prevent apoptosis?

Answer 42

NGF binds TrkA, activating PI3-K signaling, which inhibits caspase-9 and prevents apoptosis.