Quiz 2 Preparation Flashcards
T/F: The neurotransmitter that a neuron releases is not always fixed.
True
What determines the neurotransmitter that the neuron releases?
transcription factor programs– otherwise neuron will default to it’s hardwired fate
What can change neurotransmitter identity once the neurotransmitter is determined by TFP’s?
experience and target innervation
Neurotransmitter identity is plastic
Changes through rewiring and connectivity
Is a neuron’s neurotransmitter phenotype fixed or flexible?
It is hardwired but can change based on experience and target derived signals
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.
True
For Neural crest differentiation, what are the first and second this that give rise to sensory neurons?
1) Ngn2 + FoxS1 = sensory precursor
2) Ngn1 = sensory neuron
What transcription factors turn a sensory neuron into nociceptive neuron?
Runx1 and TrkA
What transcription factors turn a sensory neuron into proprioceptive neuron?
Runx3 and TrkC
How do neural crest cells differentiate?
They give rise to sympathetic and sensory neurons. Sensory neurons are fixed, while sympathetic neurons can change their fate.
If a gland secretes IL-6 cytokine, it transforms a ______ neurons fate to _______ (instead of noradrenergic)
1) sympathetic
2) cholinergic
How do peripheral targets influence neuronal fate?
Secreted signals like IL-6 can change neurotransmitter phenotype, especially in sympathetic neurons.
T/F: In CNS, neurotransmitter phenotype is less fixed compared to the periphery.
FALSE– more fixed
bHLH? (transcription factors)
Basic Helix-Loop-Helix
What are examples of bHLH?
Neurogenin and Mash1
bHLH TF are expressed in what cells?
neuroepithelial cells (not in mature neurons)
What does it mean for these TFs to be expressed in neuroepithelial cells?
CNS neurotransmitter identity is largely determined before differentiation, migration, and final specification.
Is neurotransmitter phenotype in the CNS is flexible like in the periphery
No, CNS neurotransmitter identity is more “hardwired” due to early transcription factor expression before differentiation.
Neurogenin 1 and 2 give rise to what neuroepithelial cells in the cerebral cortex?
dorsal
Mash1 give rise to what neuroepithelial cells in the cerebral cortex?
ventral
What is the concept of apoptosis?
When over half of all neurons born during development die due to programmed cell death
Why does apoptosis occur?
The brain overproduces neurons, and only those that establish proper connections survive.
What does apoptosis ensure with this process?
This ensures efficiency: neurons must compete for survival signals, eliminating excess cells that don’t form proper connections.
Why do so many neurons die during development
Neurons are overproduced, and competition for survival factors determines which ones live. This ensures efficiency and proper wiring.
T/F: Motor neurons (MNs) depend on muscle targets for survival.
True
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?
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.
How do muscle targets influence motor neuron survival?
Muscle-derived signals provide essential survival factors. More muscle tissue = more motor neuron survival.
What does blocking muscle activity do?
Increases MN survivalW
What is Curare and what does it prevent?
- a drug that blocks acetylcholine receptors in muscles
- prevents normal synaptic activity → rescues many neurons from dying
T/F: Synaptic activity normally triggers localized release of a pro-death signal from muscle, which kills about 25% of motor neurons.
True
How does synaptic activity affects motor neuron survival?
Active muscles release signals that contribute to MN death. Blocking muscle activity (e.g., with curare) rescues more MNs.
What are the three major neurotrophins?
NGF (Nerve Growth Factor)
BDNF (Brain-Derived Neurotrophic Factor)
NT-3 (Neurotrophin-3)
What is the neurotrophic factor hypothesis?
Neurons must compete for survival factors
What are neurotrophins?
Small proteins secreted by target tissues that prevent apoptosis in neurons.
Key Experiment!!
Injecting NGF into an embryo → More neurons survive.
Blocking NGF → More neurons die.
This confirms that NGF is a critical survival signal.
Why do neurons die despite being “healthy”?
They lack enough neurotrophic factors, leading to apoptosis.
Two Main Neurotrophin Receptors
Trk Receptors → Promote survival.
p75 Receptor → Promotes cell death (binds all neurotrophins with low affinity).
Survival depends on receptor activation”
If Trk is activated, neurons live.
If p75 is activated, neurons die.
How do neurotrophins influence survival?
Neurotrophins bind Trk receptors for survival, but if they bind p75 receptors, neurons undergo apoptosis.
What is the binding of NGF to TrkA activates survival pathways?
FRS2 → Ras Pathway → Promotes differentiation.
PI3-K Pathway → Promotes survival.
What are the Cell Death (Apoptosis) Pathways?
Extrinsic Pathway: Activation of death receptors on the cell surface.
Intrinsic Pathway: Mitochondria release signals to activate caspases, leading to apoptosis.
What are caspases?
Key executioners.
Caspase-9 (initiator) is inhibited by PI3-K.
Caspase-3 (executioner) completes cell death.
How does NGF prevent apoptosis?
NGF binds TrkA, activating PI3-K signaling, which inhibits caspase-9 and prevents apoptosis.