MCDB 423 Lecture 21: Lecture 21

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Molecular, Cellular and Developmental Biology
MCDB 423
John Kuwada

Lecture 21 Slide 3 We talked about development of the eye specific connection in the LGN and cortex -The paper we talked about is talking about the retinotopic map that is formed in the superior colliculus (SC) -RGC makes connections to both LGN and SC -SC is important for vision; can see it’s functional event more in frogs than in mammals (in mammals, LGN and visual cortex play a bigger role in vision) Axons from RGC target to specific layers to the LGN and LGN targets themselves to specific regions in the cortex -Parts of the circuits are very specific This paper focuses on the SC Slide 5 One of the axons is from the ipsi and the other is from the contralateral Early in development, these axons are forming branches from multiple areas of the LGN but make more connections in one layer and prune ones in other layers Slide 6 SC is very easy to see You can see that the axons at P1 are making contacting a large region of the SC -They are changing their structure (pruning) Ultimately this leads to making more specific connection to the posy-synaptic cells Slide 7 There is physical information in the SC that’s telling the axons where to go -Think about the ephrine molecules -Activity driven refinement also plays a role to create the final role RGC axons that expressed high amounts of Eph receptors had to avoid the high ephrine gradient -Ephrine drive to where the axons try to form the branches and then the activity drives them to form synapses in the same location slide 8 Hebb’s Rule: neurons that fire together are wiring together This paper explores the role of these spontaneous waves of activity that are happening in the retina -These are not experience driven -They are happening in the retina itself (can take out the retina and it is still occurring even without light stimulation) This means that cells that are far away are firing at different lengths Slide 9 If you take the retina, you can explant the retina and do Ca+2 imaging and see the waves -This is called spontaneous activity -This happens in early development of the retina -Once the circuit is fully mature, the waves don’t happen anymore Waves are visualized by multielectrode array -You have a bunch of electrodes on the grid, place the retina on top and measure the signal from the electrodes In the video, each dot represents a cell -They become bigger when an event is detected -The closer they are, the more synchronized they are Is this activity functionally important for development? -To find this out, you have to have a way to disrupt them slide 10 They used a mutation in one of the subunits of the ACh receptor Background why this works -This is a cartoon of some of the connection in the retina -These are the signal cells that make connections outside of the retina Some cells that make connections to RGC cells are amacrine cells and bipolar cells When the retina circuits are nearly formed, it’s thought that amacrine cells are connected by gap junctions -So when one fires, the others fire at the same time -This is important for the retinal waves -So we could inhibit the waves by messing with the gap junctions but this is hard to do genetically -The amacrine cells are making chologenic connections to RGC Answer: C -So the amacrine cells are driving the early waves using cholorgenic transmission -The receptors for ACh are on the RGC to respond to the input from the amacrine cells The gap junctions are transient -The ACh only play a role in the first postnatal week; the second week depends on glutomenergic transmission between the bipolar cells and RGC So this mutant allows us to disrupt retinal waves in the first postnatal week -This doesn’t disrupt the firing of the RGC, just the synchronizing firing slide 11 First post natal week is when the refinement occurs so targeting the cholinergic receptors during this time is perfect for this experiment Slide 12 When the cells get bigger, this indicates that AP occurred -But here you see (to t
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