Session 7: Evolution of Vertebrates
Transcript of Part 2: Neural Circuits and How They Evolve: A Startling Example!
00:00:07.18 Hi, my name is Melina Hale. 00:00:09.01 I'm a professor at the University of Chicago. 00:00:11.14 My lab works on 00:00:12.25 neurobiology, biomechanics, 00:00:14.09 and evolution. 00:00:16.18 In a previous video, 00:00:17.28 I gave an introduction to evolution, 00:00:20.08 and now I want to give you 00:00:22.08 an example of how we study evolution 00:00:24.02 in our lab, 00:00:25.14 and one of the things we look at is 00:00:27.20 the evolution of neural circuits. 00:00:28.27 So I'll talk about one of the systems we study, 00:00:31.28 which is the startle response, 00:00:33.12 its neural circuits, 00:00:34.20 and how we think they're evolving 00:00:36.22 over time. 00:00:37.26 So, the example on the screen here is... 00:00:41.02 you might be able to tell it's a fish. 00:00:42.07 It's actually a larval zebrafish. 00:00:44.09 It's about five days old 00:00:45.26 and three millimeters long, 00:00:47.19 and the probe you see 00:00:50.18 coming in from the left side of the screen 00:00:53.20 is a little injector and it has dye in it, 00:00:55.20 and one of the ways we get fish to startle, 00:00:58.14 to study this behavior, 00:01:00.20 is through puffing a little bit of dye at their body 00:01:02.29 and then watching their response. 00:01:04.22 So, you'll see its response. 00:01:06.13 It's analogous to a startle in humans, 00:01:09.28 which might be if you're at a scary movie 00:01:11.16 and something surprising happens, 00:01:13.08 we jump. 00:01:15.05 This is the fish equivalent of that. 00:01:16.27 It looks a bit different. 00:01:18.18 Let me show you the video 00:01:20.22 and we can talk about it a little bit. 00:01:22.12 So, that's the startle. 00:01:23.28 So, you might have been able to see the dye 00:01:25.22 hit the side of the head of the animal, 00:01:27.12 and then you see this big turn to one side, 00:01:30.04 and the animal swims away. 00:01:31.26 This is the behavior and circuit 00:01:33.24 we'll mainly be talking about today. 00:01:40.14 So, let's back up for just a minute, though, 00:01:43.09 and talk about how we study the brain. 00:01:45.29 A lot of different researchers 00:01:48.02 are working on brain function and structure, 00:01:50.16 and have been for many, many years, 00:01:52.04 and there's a lot of beautiful work going on. 00:01:54.14 Some of it tries to 00:01:56.26 identify how regions of the brain are functioning. 00:01:59.10 So, here we see half of the brain, only, 00:02:02.00 in a translucent skull, 00:02:04.13 and in red is one little part of the brain 00:02:06.29 that's called Broca's area, 00:02:08.13 and you'll see it when it comes back around, 00:02:10.02 right there. 00:02:11.12 This is actually part of the brain 00:02:13.05 that's really active when we are speaking, 00:02:15.13 so as I'm talking to you, 00:02:17.20 that part of my brain 00:02:19.20 is really, really active. 00:02:21.13 And people go and study 00:02:23.02 all these different regions of the brain 00:02:24.13 to understand when they're active 00:02:26.20 in relationship to behavior 00:02:28.28 and how they interact. 00:02:30.11 So, in addition to understanding 00:02:32.24 the cells that are in these locations, 00:02:34.12 like in Broca's area, 00:02:37.02 researchers are also trying to understand 00:02:39.15 how these cells connect. 00:02:40.26 So, the cells in the nervous system 00:02:43.13 are not just little balls 00:02:45.01 like you might see in some typical pictures of cells. 00:02:48.09 They have long processes on them 00:02:50.09 and those processes connect between cells, 00:02:53.01 from cell to cell, 00:02:54.10 and among regions of the brain. 00:02:55.24 So, what we're looking at on this image 00:02:58.01 is lots of different processes, 00:03:00.01 from regions of the brain, 00:03:01.15 from particular neurons 00:03:03.10 that are traveling to other parts of the brain 00:03:04.25 to integrate information, 00:03:06.19 to transmit information, 00:03:08.12 and ultimately to generate 00:03:11.05 some sort of function, 00:03:12.09 whether it's a behavior 00:03:13.26 or a stored memory... 00:03:15.13 various things like that. 00:03:19.21 Another way we've been studying the brain, 00:03:22.05 in addition to doing experiments 00:03:26.01 that try to look at 00:03:27.25 connections and regions, 00:03:29.25 is through wonderful neurology work 00:03:32.17 that's examined how injuries 00:03:35.03 are associated with changes 00:03:36.26 in brain function and behavior. 00:03:38.12 And that work started a very, very long time ago. 00:03:42.02 These are pages from the 00:03:43.13 Edwin Smith papyrus, 00:03:45.09 which is from about 1500 BC, 00:03:48.08 and is the first, the earliest documented 00:03:52.16 incident of people 00:03:55.15 actually relating an injury 00:03:57.18 to the nervous system, 00:03:58.26 or to the body, 00:04:00.17 to a behavior, 00:04:02.06 so seeing that there's an injury 00:04:04.03 to a part of the spinal cord or brain 00:04:05.25 and how that affects 00:04:07.21 the movements of an animal 00:04:09.08 or the behavior of a human, 00:04:11.13 in particular in this. 00:04:13.11 In my lab, we're interested in understanding 00:04:16.13 how particular neurons, nerve cells, 00:04:19.01 connect to one another, 00:04:20.11 and how those cells 00:04:22.02 and the simple circuits they're a part of 00:04:24.15 generate movements, 00:04:25.26 the startle movement in particular 00:04:27.19 that I showed you earlier. 00:04:29.08 So, to understand circuits and how they function, 00:04:32.15 a lot of us use simple model systems 00:04:35.10 for that work. 00:04:36.24 They're much simpler, 00:04:38.09 less complicated than the human brain 00:04:40.06 or large brains, 00:04:42.01 but yet they let us get at basic principles 00:04:44.15 of how the nervous system functions. 00:04:46.19 One of the fantastic models 00:04:48.16 that's been used for neural circuit work 00:04:50.23 is the nematode C. elegans. 00:04:54.16 The nematode is pictured right down here. 00:04:56.27 It's a tiny little worm, 00:04:58.26 really, really small. 00:05:00.15 It has only a small number of neurons 00:05:03.00 in its nervous system, 00:05:04.12 a few over 200, 00:05:06.19 and folks working on C. elegans 00:05:08.25 have been able to map 00:05:10.27 how those neurons connect to one another. 00:05:12.22 So, what you're seeing in these little blips 00:05:14.28 to the left of the nematode 00:05:16.20 are different neurons and their pathways, 00:05:19.03 the connections from one to the other. 00:05:23.05 Now, there are a number of other 00:05:25.08 simple model systems that have been 00:05:27.07 used productively in neuroscience 00:05:29.09 -- the sea hare on the left, 00:05:31.02 lobsters, lampreys, 00:05:32.25 and bees are just a few examples of those -- 00:05:35.15 and they've provided an understanding of 00:05:39.07 foundational principles of connectivity and function, 00:05:42.14 really important things that 00:05:44.17 have influenced a lot of work in neuroscience, 00:05:46.04 for example the work in learning and memory 00:05:48.23 in the sea hare on the left. 00:05:53.10 When you're interested in evolution, though, 00:05:55.22 as we are, 00:05:57.13 we still have some issues here. 00:05:58.23 So, we can have all of these simple models 00:06:01.03 spread across the phylogeny, 00:06:02.27 but because there's so few of them, 00:06:04.16 and they're so far apart, 00:06:06.13 trying to reconstruct 00:06:08.12 the evolutionary history of a neural circuit 00:06:11.13 is really difficult, 00:06:13.03 and we're just at the beginning stages 00:06:14.21 of being able to do that 00:06:16.16 in organisms. 00:06:19.05 The startle behavior, 00:06:21.22 for several reasons that I'll talk about 00:06:23.15 in a few minutes, 00:06:24.26 is one of the best systems 00:06:26.28 for understanding how neural circuits evolve. 00:06:29.27 Part of the reason that it's so useful 00:06:32.09 is that because the startle behavior 00:06:34.10 occurs in so many animals 00:06:36.12 across the phylogeny, 00:06:37.28 it's a key predator avoidance behavior, 00:06:40.04 so you might imagine, evolutionarily, 00:06:42.06 it's going to be very important and highly conserved. 00:06:45.17 What we're looking at here is 00:06:48.05 a pike, a northern pike, 00:06:50.23 the image on the right, 00:06:52.10 and what you're seeing on the left is a still from a video 00:06:54.11 that I'll show you in a second. 00:06:55.28 Just to orient you to that video, 00:06:57.12 we're actually looking at the belly of the fish, 00:06:59.19 the ventral view, 00:07:01.15 and that gray shadow above it 00:07:03.12 is my hand coming over, 00:07:05.05 and I'm going to startle this animal. 00:07:07.22 So, if we look at the movie of that behavior, 00:07:10.16 you'll see how the pike startles, 00:07:14.12 so let's... it's going... 00:07:16.24 there, I've touched the fish on the head 00:07:18.28 and you can see it do that really fast movement away, 00:07:21.22 like the larval zebrafish 00:07:23.26 in the first image that I showed you. 00:07:26.13 Now, this type of startle, 00:07:28.07 this bend to one side and swim away, 00:07:31.10 is characteristic of many, many species of fish. 00:07:34.17 If we look at in just a set of silhouettes, 00:07:38.10 we can really break down what that behavior is. 00:07:42.08 Generally, these fish start 00:07:44.02 in a straight position, 00:07:45.20 so as they're sitting in the water 00:07:47.08 not expecting a predator to come along, 00:07:49.01 they're just hanging out and their body is straight. 00:07:51.08 When the sense a predator coming from one side, 00:07:53.20 as shown in image three, 00:07:55.11 they do this massive turn and bend, 00:07:58.13 they orient their head away from the predator, 00:08:01.22 and then they use a number of swimming strokes 00:08:04.09 to get out of there as fast as they can. 00:08:06.29 This is a typical response, as I said, 00:08:09.16 of a number of fish including zebrafish, 00:08:11.20 and pike, and many others. 00:08:15.18 Now, what's driving that behavior? Let me tell you a little bit about the 00:08:19.17 neural circuit that's important 00:08:22.02 for that response. 00:08:24.11 The circuit is highly conserved, 00:08:26.07 so we see some of the same neurons 00:08:28.22 in pike, and in zebrafish, 00:08:30.10 and all the other species, 00:08:31.21 even though they're hundreds of millions of years 00:08:34.27 separated in evolutionary time, 00:08:37.11 in terms of when they diverged. 00:08:39.19 So, this is... 00:08:41.29 you might not be able to tell right away, 00:08:43.25 but this is the brain of the zebrafish, 00:08:46.02 with certain neurons labeled. 00:08:48.00 So, just to orient you... 00:08:49.19 here are the eyes and the ears of the brain, 00:08:53.00 the otic capsules, 00:08:54.23 and all those white blips 00:08:56.17 are different nerve cells 00:08:58.14 that are in the brain 00:08:59.26 and are sending those processes, 00:09:01.15 what are called axons, 00:09:02.29 down into the spinal cord of the animal. 00:09:04.20 So, they're sending signals 00:09:06.11 down to the body 00:09:07.26 to get the fish to do something. 00:09:09.16 This is a larval zebrafish, 00:09:11.20 so the head is only a millimeter or so across. 00:09:14.07 Now, these, here, are really important cells 00:09:18.13 for the startle response. 00:09:20.05 They're called the Mauthner neurons 00:09:21.23 and there are only two of them. 00:09:23.17 They're giant neurons that are in 00:09:26.07 all of these fish 00:09:27.23 that do this type of startle that I've shown you, 00:09:30.12 and they're located in the hindbrain of the animal. 00:09:34.13 Up here are a different set of neurons 00:09:36.23 we won't be talking about, 00:09:38.04 but they're neurons in the midbrain 00:09:39.21 that control that rhythmic swimming 00:09:41.17 that you might have seen at the end of the videos 00:09:44.00 that I showed you. 00:09:45.19 So we're going to focus on the Mauthner cell 00:09:47.21 and the Mauthner cell circuit. 00:09:50.08 So, this is a simplified 00:09:52.08 Mauthner cell circuit, 00:09:53.23 so the Mauthner cell 00:09:55.10 and the neurons that it connects to. 00:09:56.28 I just wanted to show you a little bit about 00:09:59.09 how it works in the organism. 00:10:01.09 So, if we have a stimulus in the circuit, 00:10:03.07 coming from the right, 00:10:04.28 then here's the circuit... 00:10:06.17 the stimulus is coming from the right... 00:10:08.03 the Mauthner cell on the right, 00:10:10.04 which is this big, dark blue cell, 00:10:12.12 is going to fire. 00:10:13.29 When it fires, it's actually generating 00:10:16.14 what's called an action potential, 00:10:18.01 a signal that's transmitted 00:10:19.28 all the way down its process, 00:10:21.12 down its axon. 00:10:22.25 In this case, it goes 00:10:25.06 from being in the hindbrain, 00:10:26.18 which is that top group of cells on this image, 00:10:28.16 down into the spinal cord. 00:10:30.11 In the spinal cord, 00:10:32.21 it'll signal other interneurons and motor neurons 00:10:35.16 to signal muscle 00:10:37.11 to cause the body bending 00:10:39.03 that I showed you in those videos. 00:10:40.17 So, if I'm the fish 00:10:42.14 and this is, you know, this is me, 00:10:44.17 a stimulus coming from this side of my head 00:10:46.19 would cause the Mauthner cell to fire, 00:10:49.19 it would send a signal down my spinal cord, 00:10:52.03 and I would bend in that direction, 00:10:54.16 forming that C-shaped bend 00:10:56.12 that you saw in those videos. 00:11:00.28 Now, one of the really interesting things 00:11:04.03 about the Mauthner cell 00:11:05.19 is that there's this special part of the circuit 00:11:08.03 that's really not diagrammed in detail here. 00:11:10.07 It's called the axon cap, 00:11:12.09 and the axon cap has all sorts of interesting things 00:11:14.20 going on in it. 00:11:16.00 It has cells coming in 00:11:17.22 that excite the Mauthner cell 00:11:19.03 and get it to fire more readily. 00:11:20.18 It also has neuron processes coming in 00:11:24.15 that inhibit the Mauthner cell 00:11:26.07 and prevent it from firing. 00:11:27.19 So, there's a lot going on in this region. 00:11:30.02 Because the Mauthner cell 00:11:31.23 is so big and obvious, 00:11:33.26 and so conserved across a lot of taxa, 00:11:36.16 we can use the cell as an anchor 00:11:39.15 to understand the circuit components 00:11:41.27 that are in the axon cap structure. 00:11:46.18 So, let me show you a Mauthner cell firing 00:11:49.19 and then we'll talk a little bit more about it. 00:11:52.28 So, this is a Mauthner cell 00:11:55.02 that I've injected with 00:11:56.24 what's called a calcium-sensitive dye. 00:11:59.00 So, when the Mauthner cell fires, 00:12:01.22 calcium floods into the cell, 00:12:03.27 and the dye actually 00:12:05.27 reacts with the calcium 00:12:07.13 and becomes brighter when the cell is active. 00:12:10.09 Now, we've color-coded brightness 00:12:12.06 with this heat map, 00:12:13.21 so that when this cell fires 00:12:15.20 you'll see more reds and oranges. 00:12:19.01 So, here's the Mauthner cell 00:12:20.17 and you can imagine I'm tapping the fish on the head 00:12:23.07 from this side, 00:12:24.17 and you can see what happens. 00:12:27.16 So, that's a Mauthner cell activation; 00:12:30.16 that's the activity 00:12:32.18 that's initiating that big bend 00:12:34.18 that we showed you. 00:12:37.07 Let me show you one more time... 00:12:39.04 touch the fish 00:12:41.05 and it fires really, really quickly. 00:12:42.29 Something I didn't point out before 00:12:44.25 is that these various videos I've shown you, 00:12:46.14 and even this image, 00:12:48.00 are shown slowed down quite substantially. 00:12:50.14 A typical Mauthner cell response... 00:12:53.25 the behavior would occur 00:12:55.29 within tens of milliseconds, 00:12:58.02 so in less than the blink of an eye. 00:13:02.00 So, studying the Mauthner cell overall, 00:13:04.23 and this is not my lab specifically, 00:13:06.18 but in this broad group of researchers 00:13:08.24 that have looked at the Mauthner cell 00:13:10.18 over 100+ years, 00:13:12.09 we've learned a lot about neuroscience. 00:13:14.20 This simple system has been really, really valuable. 00:13:17.22 We've looked and been able to understand 00:13:19.24 more about the subcellular structure 00:13:21.18 of vertebrate neurons, 00:13:23.10 how neurons communicate to each other 00:13:25.13 through different types of synapses. 00:13:28.05 We've learned about this transmission 00:13:30.01 of electrical signals between neurons as well. 00:13:33.26 In addition, the Mauthner circuit 00:13:35.28 has been used to study learning 00:13:38.06 and to look at the relationship 00:13:40.00 between neural activity and behavior. 00:13:43.00 So, it's given us access to circuits 00:13:45.16 in a way that we just can't get 00:13:47.17 in a human brain, for example. 00:13:50.29 Alright, so let's talk a little bit 00:13:53.24 about evolution of this circuit now. 00:13:56.02 So, I introduced you to the Mauthner cell 00:13:58.12 and told you that's found 00:14:00.03 in lots of different animals, 00:14:01.24 and I also mentioned this structure 00:14:03.12 called the axon cap, 00:14:04.24 which has excitatory inputs and inhibitory inputs, 00:14:07.05 and gives us a little window 00:14:09.04 into how neural circuits might work. 00:14:11.12 So, this is a phylogeny 00:14:13.12 that I showed on the previous video 00:14:15.08 that I did on an introduction to evolution. 00:14:18.20 It's again of just vertebrate animals, 00:14:21.01 and only a very, very few of them 00:14:23.10 where we see on the left 00:14:25.09 the jawless fishes, like lampreys. 00:14:27.21 We move up the tree through the chondrichthyans 00:14:30.02 into fishes, 00:14:32.06 and then tetrapods as well. 00:14:34.29 Now, for the Mauthner cell, 00:14:36.22 we see its presence 00:14:39.02 in many of these different groups. 00:14:41.00 Lampreys have the Mauthner cell. 00:14:42.24 Chondrichthyans, in a few species we see Mauthner cells. 00:14:46.04 Many, many fishes, 00:14:48.00 the vast majority of the 30,000 species of fishes 00:14:51.02 that are known have Mauthner cells. 00:14:53.11 And even in amphibians, 00:14:55.15 in both tadpoles and in some frogs, 00:14:57.25 as well as in salamanders, 00:14:59.10 we also see Mauthner cells. 00:15:02.04 When we move up into the tree, though, 00:15:04.20 we have quite a mystery to solve. 00:15:06.29 We do not know what happens 00:15:09.10 to these giant, really important neurons 00:15:12.05 once we move up into the tetrapod animals 00:15:15.24 that have become terrestrial 00:15:17.16 and have changed their startle behaviors. 00:15:19.12 It's one of these big questions 00:15:21.27 that I'm so curious about and my lab's trying to investigate. 00:15:27.10 So, let's look at that cap 00:15:29.05 and see where we've gotten 00:15:30.20 in terms of understanding how the Mauthner cells 00:15:32.07 and their circuits have evolved. 00:15:34.27 So, remember where those yellow stars were 00:15:37.12 on that very simplified diagram 00:15:39.04 of the Mauthner circuit. 00:15:40.13 This is what we're looking at here on the left, 00:15:42.19 that cap structure, 00:15:43.29 and as I mentioned there are excitatory neurons 00:15:46.23 that are connecting to the Mauthner cells. 00:15:48.15 Those are shown as these cells that are... 00:15:50.29 this process that's spiraling around the base 00:15:53.19 of the cell on the far left. 00:15:55.17 Then we see this sort of egg-shaped capsule 00:15:57.26 around that process of the cell, 00:16:01.09 and those little black nubbins coming in 00:16:04.17 are the inhibitory interneurons, 00:16:06.05 that are shutting down the Mauthner cells. 00:16:07.27 So, we have excitatory and inhibitory components. 00:16:11.01 On the right, you can see what that actually looks like 00:16:14.06 in a section of a brain of one of these fishes. 00:16:17.02 So, this is what we call the composite axon cap. 00:16:19.09 It has all these different components to it. 00:16:21.20 This is the cap that you would see 00:16:24.09 in fish that... 00:16:25.26 if you go to an aquarium 00:16:27.11 and are looking at a lot of fish swimming around in a tank, 00:16:29.20 or at a pet store, 00:16:31.04 most of them have Mauthner cells that look like this. 00:16:35.10 Now, I showed you this image of the startle 00:16:38.16 in the top panel, here, 00:16:40.12 this is shown in a trout, 00:16:42.15 and the composite cap and Mauthner cell 00:16:45.08 generates this type of startle. 00:16:47.14 But startles in fish are actually 00:16:48.28 a bit more diverse than that, 00:16:50.25 and in particular if we look down in the lampreys, 00:16:52.28 which diverged off the of the main lineages of vertebrates 00:16:55.22 at the base of the tree, 00:16:57.01 we see a very different type of startle. 00:16:59.08 It's a retraction response, 00:17:00.28 shown down below here, 00:17:02.22 where the animal, actually, when stimulated, 00:17:05.24 kind of contracts or accordions its body. 00:17:08.17 In the lampreys, the Mauthner cells 00:17:11.05 are there, 00:17:12.20 but they don't have this axon cap structure, 00:17:14.16 so without these inputs 00:17:16.12 they generate a very, very 00:17:18.14 different behavioral output. 00:17:23.22 So, here are the two primary basic 00:17:27.16 types of caps that have been known for awhile: 00:17:30.12 this composite cap of typical teleosts fishes, 00:17:32.29 typical bony fishes, 00:17:34.11 and this no cap condition 00:17:36.11 that we see in these retracting animals like lampreys. 00:17:41.06 In my lab, 00:17:43.11 one of my students, Hilary Bierman, 00:17:45.01 and a colleague, Steve Zottoli, 00:17:47.06 worked with me to try to get 00:17:49.11 a better sense of how this cap structure 00:17:51.25 varies across species, 00:17:53.17 and whether there is actually variation 00:17:55.29 between those two basic morphs. 00:17:58.05 When we look at lots and lots of different species, 00:18:00.25 we actually found that there are 00:18:03.11 four types of caps. 00:18:04.21 In addition to those first two that I talked about, 00:18:06.22 we have what's called a simple cap, 00:18:08.14 that's shown on the top, 00:18:10.03 where we have those winding excitatory fibers 00:18:12.19 at the base of the Mauthner cell, 00:18:14.19 and then we have what we're calling 00:18:17.05 a simple dense cap, 00:18:18.13 where we have those same winding fibers, 00:18:20.21 but they're much, much more populous, 00:18:22.17 much denser in the axon cap region. 00:18:25.26 Note both of these cases, 00:18:27.20 and these images in the diagrams shown here, 00:18:30.09 we don't have that nice glial... 00:18:35.04 that nice cap around the axon 00:18:37.13 where we have those inhibitory interneurons coming in, 00:18:40.07 so they differ quite a bit from the composite cap. 00:18:43.26 So, let's map the Mauthner cells 00:18:46.10 and the Mauthner cell axon cap 00:18:47.27 onto the phylogenetic tree of vertebrates, 00:18:51.07 and this is a bit more of a complicated tree, 00:18:53.11 a detailed tree, 00:18:54.29 than what I've shown you previously. 00:18:56.19 At the base, shown in yellow, 00:18:58.23 are two clades that actually even aren't vertebrates. 00:19:01.08 We see the amphioxus there 00:19:03.15 and hagfishes. 00:19:05.05 Amphioxus and hagfish 00:19:06.24 actually don't even have Mauthner cells. 00:19:08.09 We think the Mauthner cells 00:19:10.05 arose before the lampreys, 00:19:12.03 which are shown in white, 00:19:14.03 branched from the rest of the vertebrates. 00:19:16.00 Now, as I said previously, 00:19:18.06 the lampreys do this retraction response 00:19:19.17 and they don't have axon caps at all. 00:19:23.07 As we move up the tree, 00:19:24.11 we see several lineages 00:19:26.11 that are shown in purple 00:19:27.29 that have a simple cap structure 00:19:30.07 that I showed you. 00:19:32.06 Those includes things like sharks 00:19:34.17 and, as we move up, amphibians and lungfish, 00:19:37.08 as well as some of the basal bony fishes 00:19:40.08 called bichers and ropefishes. 00:19:43.14 Moving up in the tree from there, 00:19:45.07 we see the evolution of the simple dense cap, 00:19:47.28 and that's in these species 00:19:50.23 that we don't actually have a lot of extant today, 00:19:53.13 they are some species, but not a ton, 00:19:55.23 of sturgeons and gar, 00:19:57.29 and there's really only one extant species 00:20:00.03 of bowfin 00:20:02.01 that was a very diverse group 00:20:03.21 many, many hundreds of millions of years ago. 00:20:07.03 They all have a simple dense cap. 00:20:09.23 Interestingly, where we see a transition 00:20:13.06 into this composite complex cap structure, 00:20:17.12 is right at the base of the teleosts. 00:20:19.22 Now, the teleosts are the modern bony fishes. 00:20:22.13 It's this amazingly diverse 00:20:25.08 and speciose group. 00:20:26.26 There are many, many species. 00:20:28.17 It's the dominant group of fishes 00:20:31.16 in the world today, the extant fishes. 00:20:34.03 Nearly all of them 00:20:36.04 have this composite cap. 00:20:37.20 It seems to be characteristic of that group of organisms. 00:20:41.21 Now, evolution isn't quite that simple, 00:20:43.17 and we do see some differences 00:20:46.01 from this nice pattern 00:20:48.13 that we've looked at up the tree. 00:20:50.08 In particular, if you go back over into the purple area, 00:20:53.11 where the sharks are, 00:20:55.02 a branch in that tree called the ratfish, 00:20:56.19 or the chimeras, 00:20:58.08 have a simple cap. 00:20:59.21 And in the teleosts, 00:21:01.11 you can see that one white branch 00:21:03.06 and that's the eels. 00:21:05.13 And so in a few places through the tree, 00:21:07.19 we will see variation. 00:21:09.23 Now, if we look at how 00:21:14.08 the cap structure and this variation 00:21:16.02 relate to behavior, 00:21:17.21 if we map behavior onto this tree, 00:21:19.14 we can pull out a couple key points. 00:21:21.28 The first is that when we have 00:21:24.24 the absence of this axon cap, 00:21:26.10 you just have the Mauthner cells 00:21:28.00 with none of this excitatory and inhibitory inputs 00:21:30.07 coming to them, 00:21:31.19 we tend to see a retraction response, 00:21:33.20 which is that pulling back of the head. 00:21:38.01 We see that in lampreys 00:21:39.15 and also in the eels, 00:21:41.01 which lack the axon cap structures. 00:21:47.01 All of these other animals 00:21:48.25 perform more of a C-start type of response, 00:21:51.23 although it varies in its strength 00:21:53.29 and how high performance, 00:21:56.11 how fast it is. 00:21:58.00 But one thing that's noticeable 00:22:00.17 is that when we get to this composite cap 00:22:01.28 at the base of teleosts, 00:22:03.13 we see a really high performance response, 00:22:06.20 like there's some innovation 00:22:08.17 of how that cap works 00:22:10.10 that allows the performance 00:22:12.01 to be very, very high, a very strong response. 00:22:15.11 This middle area of the tree, 00:22:17.05 we're still figuring out. 00:22:18.27 Fish with the simple and simple dense caps 00:22:21.08 have more diverse startles 00:22:23.11 - the same basic pattern, 00:22:24.20 but there's a diversity in performance 00:22:26.22 and how it's generated by muscle 00:22:28.13 that we're still trying to understand. 00:22:30.17 And the motor patterns are quite complex. 00:22:34.26 Now, if we get up into the amphibians, 00:22:36.25 as you could imagine, 00:22:38.19 I mentioned earlier that 00:22:40.13 not only do the tadpoles 00:22:42.22 have Mauthner cells, but also frogs. 00:22:45.05 You probably can, you know, 00:22:46.25 predict what a frog's startle response would be, 00:22:49.17 it will be a bilateral hop. 00:22:51.17 One of the things we're trying to figure out now 00:22:54.01 is how that relates to the Mauthner cells 00:22:55.27 and this circuit. 00:22:57.17 Well, what about the startles 00:22:59.01 of humans and other mammals? 00:23:00.08 This is an example 00:23:02.01 of an armadillo startle, 00:23:04.04 where the animal jumps up on its legs 00:23:06.13 into the air when it's startled. 00:23:08.11 Are these types of behaviors, and our startles, 00:23:10.27 also generated by Mauthner cells 00:23:13.03 and this Mauthner cell circuit? 00:23:14.27 We actually don't know. 00:23:16.23 There are similarities in the startle behavior, 00:23:18.27 as you might imagine. 00:23:20.17 They're really fast, really high performance, 00:23:22.23 but they're different 00:23:24.05 and we haven't been able 00:23:25.25 to associate the neural circuit of the startle in mammals 00:23:28.20 with that of the startle of fishes. 00:23:31.23 It's one of the things we really want to know in my lab, 00:23:34.24 and we're beginning to take steps 00:23:38.07 to figure out. 00:23:41.05 So, let's conclude. 00:23:43.16 First, I want to make the point that 00:23:46.25 there are a lot of ways of understanding 00:23:48.16 how the brain works, 00:23:49.27 lots of labs doing beautiful imaging work 00:23:51.25 studying healthy human brains, 00:23:54.05 and also studying injured human brains, 00:23:56.04 where we can associate damage 00:23:58.11 to a particular region 00:24:00.03 with changes in behavior or function. 00:24:02.20 In addition, we can use more tractable brains, 00:24:04.29 or more tractable nervous systems, in other species, 00:24:07.21 like C. elegans and the sea hare, 00:24:11.15 to understand how circuits are put together. 00:24:14.14 Looking at those simple circuits, 00:24:16.17 we can use them to understand 00:24:19.05 basic principles 00:24:20.25 that also may apply in tetrapods 00:24:22.27 and in other vertebrates. 00:24:25.10 Now, in addition to using models, 00:24:27.25 comparing across models 00:24:29.25 or other species 00:24:31.05 gives us a different sort of power 00:24:32.21 of looking at how things are similar 00:24:34.20 or how evolution may have 00:24:36.15 come up with different solutions 00:24:38.19 to generating certain functions in the body 00:24:40.22 and in the brain. 00:24:42.02 So, we use comparisons and evolutionary approaches 00:24:44.20 to relate structure and function more broadly. 00:24:48.02 Now, on the Mauthner cell system in particular... 00:24:51.18 I hope I've shown you that the Mauthner cell 00:24:53.19 is an example of a simple neural circuit 00:24:56.21 that we can use 00:24:58.25 to understand not only basic principles of the nervous system, 00:25:01.19 but also nervous system evolution. 00:25:04.17 In particular, because we can follow this cell 00:25:07.09 and use it to anchor this circuit, 00:25:09.21 through brains from a wide variety of animals, 00:25:12.05 we're able to then track the circuit 00:25:14.29 over a large swath of evolutionary time, 00:25:17.19 from the divergence of lampreys on up, 00:25:20.02 and that diverge occurred 00:25:21.26 about 500 million years ago, 00:25:23.10 so we're talking about a really long time frame here. 00:25:28.29 So, as I end, I just want to acknowledge 00:25:30.19 some of the people who were important to this work. 00:25:32.27 In particular, some of my students. 00:25:35.25 These are all students who were in the lab 00:25:38.01 over the past decade or so. 00:25:40.11 Hilary Bierman, who was a graduate student, 00:25:42.13 and Rachel Fremont and Julie Schriefer, 00:25:44.01 who were both undergraduates 00:25:45.19 at the University of Chicago. 00:25:47.05 In addition, my collaborators 00:25:48.20 at the University and at other institutions, 00:25:50.29 include Steve Zottoli, 00:25:52.20 Mark Westneat, John Long, 00:25:54.00 and Vicky Prince, 00:25:55.11 and they've all been important to the ideas 00:25:57.00 as well as the data collection and analysis of this work. 00:26:00.25 In particular, though, I'd also like to thank Glenn Northcutt. 00:26:03.07 The images of axon caps that I showed you... 00:26:06.11 some of them were made in my lab, 00:26:07.27 others were actually photos of collections 00:26:10.19 that he's taken over a number of years, 00:26:13.01 and they've been so important for our work, 00:26:15.07 so I wanted to thank Glenn, 00:26:16.15 and also to make the point that collections, 00:26:19.26 biological collections, 00:26:21.23 are just really important, 00:26:23.15 not only for what we've learned up 'til now, 00:26:25.07 but for the future of discovery in science. 00:26:28.17 And of course I want to thank our funders, 00:26:31.04 the National Science Foundation, 00:26:33.23 and grants that we've had for work in the lab, 00:26:35.13 have been really important 00:26:37.19 to our research and our ideas. 00:26:39.10 So, thank you.