Lecture 7: Trophic Factors Flashcards
What are the types of synaptic refinement?
- Changes in synaptic capacity
- Synaptic rearrangement
- Synaptic segregation
What are critical periods?
developmental time when large scale changes in innervation patterns can still be made
What are ocular dominance columns?
innervation patterns in the visual cortex
Do critical periods occur in adult stages?
no - plasticity restricted to local changes in synapatic efficacy
What are the hypotheses on critical period endings?
- Plasticity diminishes when axon growth stops
- Plasticity decreases when synaptic transmission matures
- Plasticity decreases when cortical activation is constrained
- Astrocytes may also regulate closing of the critical period
When does apoptosis largely occur?
After axons have reached their targets
What cells in the ventricular zone show high levels of apoptosis, and during which part of development?
Progenitor cells
Late development
Why is apoptosis important?
Essential for neural development
- defects caused by lack of apoptosis is lethal
- too much apoptosis is also lethal
How is apoptosis regulated?
Trophic factors
- regulate neuronal survival and allow selective elimination of neurons
What are trophic factors?
- survival factors
- provided in limited quantities
- necessary for maintenance of neuronal connection and neuronal survival
How/where do neurons receive trophic factors from?
- Target tissues (retrograde signaling)
- Synaptic inputs (anterograde signaling)
- Neighboring neurons (paracrine)
- Distant cells (circulatory system)
- Glial cells
What is nerve growth factor (NGF)?
trophic factor
- produced by target tissues of sympathetic neurons
- regulates body homeostasis
What dictates number of innervating motor and sensory neurons?
target tissue
- more target tissue, more DRG and motor neurons
In the discovery of NGF, what factors aided in identification, and what happened when they were applied?
snake venom, tumors (and purified proteins from both)
- application causes axon outgrowth
When do sympathetic neurons undergo programmed cell death?
Within 24-48 hours after NGF withdrawal
What happens after NGF withdrawal?
mitochondrial cell death program activated
What happens when cytochrome C released from mitochondria?
Caspases activated, which initiate cell death
This trophic factor is critical for sympathetic ganglia to develop properly
NGF
T/F: NGF is essential for neuronal proliferation in sympathetic ganglia
False
- NGF essential for neuronal survival, not proliferation
What are neurotrophics?
subset of neurotrophic factors that have similar structures
ex: NGF
What is the structure of neurotrophin?
growth factors like NGF produced as pro-peptides (~250 amino acid long protein), processed post-translationally and cleaved (~120 amino acid peptide final product)
What ligands share conserved protein sequences?
NGF, NT-3, BDNF, NT-4/5
- share 50% protein homology
What neurotrophin receptors do the neurotrophin ligands bind to?
NGF -> TrkA
NT-3 -> TrkA, TrkC, TrkB
BDNF and NT-4/5 -> TrkB
Neurotrophins from target tissues are essential for…
- local processes in the axon terminal that support axon maintenance
- distant processes in the cell body that support neuron survival
