MCDB 423 Lecture 22: Lecture 22

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Molecular, Cellular and Developmental Biology
MCDB 423
John Kuwada

Lecture 22 Slide 1 The two axons are firing together while the blue is firing by itself -They are competing for territory This is called Hebb’s rule -Development of many features of our nervous system where the fire together wire together is seen How does it work on a cellular level? -Still a big question in neuroscience -For the post synaptic cell, you need it to respond distinctly to input from the synchronized axons Slide 2 NMDA receptors function as coincidence detectors -Nice position to make distinct signals when the neuron is getting a strong input from synchronized axons -These receptors are voltage gated so they can only open when the neuron is depolarized so you need a strong enough stimulus -This is a good way to distinguish from a strong input from a weak input slide 3 This experiment tells us that NMDA receptors are important for segregation With the three eyed frog, you generated a situation where axons from multiple eyes are competing with each other for space in the frog -Normally the eyes go their own ways and there is no competition -But the third eye is now trying to take this space and competing with the other eyes -This causes the axons to segregate and wire together If you introduce NMDA receptor inhibitors, you mess up this segregation Slide 4 Answer: C The RGC have to fire in a coordinated fashion for this to occur -So if you inhibit the ACh receptors, they can no longer be coordinated (discussed previously) slide 5 What about retrograde piece of information? Slide 6 Nitric oxide synthases can be regulated by Ca+2 -NO is a diffusible gas and can diffuse to the presynaptic neuron -Can help regulate the efficiency of synaptic vesicle recycling -This is a way to mediate changes in synapses Another good candidate are endocannabanoid molecule -They are organic compounds that are synthesized by enzymes in our neurons -The THC in weed have a similar action in this by binding to the receptors which is expressed on neurons -In this model of retrograde signaling, the enzymes are activated by Ca+2 -They can be triggered out of the cell and bind to receptors on other neurons and modulate their synaptic activity -Good candidate for refinement slide 7 BDNF is a neurotrophic factor -It’s a small protein that is secreted by many cells in the nervous system -Supports neuronal life and when it binds to receptors, it can trigger multiple changes in neurons -Can be secreted locally from dendritic spines -Secretion is stimulated by synaptic activity by Ca+2 and NMDA receptor activation slide 8 FGF is secreted from dendrites and can act locally upon axons Slide 9 The blue axon is the axon that is lost You could deprive visual input in a young animal which would have a dramatic affect on the visual development but when you do it on an adult there is no effect -What is different about the adult nervous system from the developing nervous system that allows for this plasticity in the developing nervous system? What defines the critical period? Slide 10 The brain is more than just neurons making connections with each other Gilial cells are those that aren’t neurons -We have more gilial than neurons This is an image of a developing hippocampus of the mouse For every neuron, there are about 3 astrocytes Slide 11 This is a cartoon of astrocytes -Star shaped cells They have many activities we know about -They can make contact with blood vessels to regulate blood flow and oxygen supply to the brain -They can make contact with synapses to sent NTs to neurons slide 12 In the mature brain, most synapses in the brain (especially glutamatergic) are wrapped by astrocytes Slide 13 Astrocytes play a role in forming synapses Here astrocytes are appearing in the superior calicus -There’s a huge appearance of astrocytes during the critical period of refinement They used a system to purify RGC and culture them by themselves -They developed a serum free medium to culture RGC -They grow axons nicely but they don’t preform synapses -But if you include astrocytes with them, they form many synapses -You can also do this with an astrocyte conditioned media (grow astrocytes in a media and then take that media and put that with t
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