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.