BIOL 2P94 Lecture Notes - Lecture 18: Growth Factor, Synaptic Plasticity, Cytochrome C

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Outline of Lecture 18 (02-21 E; Ginty)
Development IV
I. Function and mode of cell death in nervous system development
- 4 functions of cell death: systems matching, error correction, sexual dimorphism, remove
transient cells
- Neuron death generally occurs during target recognition due to lack of trophic support from
target tissue
- Neurotrophic hypothesis: competition over limited supply of neurotrophic factor from target
tissue leads to death of incorrectly targeted neurons
- Many cells provide trophic support, but the major ones are target-derived
- Glial cells also die during development, perhaps requiring trophic support from axons
II. Cell biology of apoptosis (general)
- Apoptosis is ATP-dependent and is clean and controlled; necrosis is not
- C. elegans worm is a classis system to study apoptosis; its genes are highly homologous to
vertebrate apoptotic genes
- Understand the role of Bcl-2, Bax, cytochrome C, APAF1, and caspases (Fig. 8 in notes)
III. Nerve Growth Factor (NGF) is the prototypical neurotrophic growth factor
- There are many families of growth factors that affect neurons; NGF will be our focus
- The NGF receptor is a RTK, and can signal through many 2nd messenger pathways; it can
activate Bcl-2, an inhibitor of apoptosis
- Expression of receptor subtypes and responsiveness to growth factors are restricted to particular
populations of neuronal and non-neuronal cells
IV. Synapse formation and elimination
- Presynaptic diffn: not much is known
- Postsynaptic diffn: in case of motoneurons, two methods of AChR clustering
1) nerve-induced clustering at synapse, regulated by agrin
2) increased AChR txn by subsynaptic nuclei, regulated by neuregulin
- Synapse elimination (not the same as cell death) ensures each myotube is innervated by only one
motoneuron
- Precise mechanism of synapse elimination is not known, but synaptic activity decreases
possibility of elimination
- This is called activity dependent synaptic plasticity, perhaps underlies memory and learning
Summary of major points
- See objectives on p. 1
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