[Script Info] Title: [Events] Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text Dialogue: 0,0:00:00.36,0:00:04.36,Default,,0000,0000,0000,,This is a thousand-year-old drawing of the brain. Dialogue: 0,0:00:04.36,0:00:06.27,Default,,0000,0000,0000,,It's a diagram of the visual system. Dialogue: 0,0:00:06.27,0:00:09.02,Default,,0000,0000,0000,,And some things look very familiar today. Dialogue: 0,0:00:09.02,0:00:13.38,Default,,0000,0000,0000,,Two eyes at the bottom, optic nerve flowing out from the back. Dialogue: 0,0:00:13.38,0:00:15.50,Default,,0000,0000,0000,,There's a very large nose Dialogue: 0,0:00:15.50,0:00:18.82,Default,,0000,0000,0000,,that doesn't seem to be connected to anything in particular. Dialogue: 0,0:00:18.82,0:00:20.52,Default,,0000,0000,0000,,And if we compare this Dialogue: 0,0:00:20.52,0:00:22.60,Default,,0000,0000,0000,,to more recent representations of the visual system, Dialogue: 0,0:00:22.60,0:00:25.55,Default,,0000,0000,0000,,you'll see that things have gotten substantially more complicated Dialogue: 0,0:00:25.55,0:00:27.12,Default,,0000,0000,0000,,over the intervening thousand years. Dialogue: 0,0:00:27.12,0:00:30.09,Default,,0000,0000,0000,,And that's because today we can see what's inside of the brain, Dialogue: 0,0:00:30.09,0:00:32.57,Default,,0000,0000,0000,,rather than just looking at its overall shape. Dialogue: 0,0:00:32.57,0:00:36.55,Default,,0000,0000,0000,,Imagine you wanted to understand how a computer works Dialogue: 0,0:00:36.55,0:00:39.73,Default,,0000,0000,0000,,and all you could see was a keyboard, a mouse, a screen. Dialogue: 0,0:00:39.73,0:00:42.12,Default,,0000,0000,0000,,You really would be kind of out of luck. Dialogue: 0,0:00:42.12,0:00:44.17,Default,,0000,0000,0000,,You want to be able to open it up, crack it open, Dialogue: 0,0:00:44.17,0:00:46.01,Default,,0000,0000,0000,,look at the wiring inside. Dialogue: 0,0:00:46.01,0:00:47.88,Default,,0000,0000,0000,,And up until a little more than a century ago, Dialogue: 0,0:00:47.88,0:00:49.88,Default,,0000,0000,0000,,nobody was able to do that with the brain. Dialogue: 0,0:00:49.88,0:00:51.76,Default,,0000,0000,0000,,Nobody had had a glimpse of the brain's wiring. Dialogue: 0,0:00:51.76,0:00:54.71,Default,,0000,0000,0000,,And that's because if you take a brain out of the skull Dialogue: 0,0:00:54.71,0:00:56.40,Default,,0000,0000,0000,,and you cut a thin slice of it, Dialogue: 0,0:00:56.40,0:00:58.89,Default,,0000,0000,0000,,put it under even a very powerful microscope, Dialogue: 0,0:00:58.89,0:01:00.08,Default,,0000,0000,0000,,there's nothing there. Dialogue: 0,0:01:00.08,0:01:01.69,Default,,0000,0000,0000,,It's gray, formless. Dialogue: 0,0:01:01.69,0:01:04.29,Default,,0000,0000,0000,,There's no structure. It won't tell you anything. Dialogue: 0,0:01:04.29,0:01:07.15,Default,,0000,0000,0000,,And this all changed in the late 19th century. Dialogue: 0,0:01:07.15,0:01:11.02,Default,,0000,0000,0000,,Suddenly, new chemical stains for brain tissue were developed Dialogue: 0,0:01:11.02,0:01:13.83,Default,,0000,0000,0000,,and they gave us our first glimpses at brain wiring. Dialogue: 0,0:01:13.83,0:01:15.85,Default,,0000,0000,0000,,The computer was cracked open. Dialogue: 0,0:01:15.85,0:01:18.70,Default,,0000,0000,0000,,So what really launched modern neuroscience Dialogue: 0,0:01:18.70,0:01:20.67,Default,,0000,0000,0000,,was a stain called the Golgi stain. Dialogue: 0,0:01:20.67,0:01:22.55,Default,,0000,0000,0000,,And it works in a very particular way. Dialogue: 0,0:01:22.55,0:01:25.66,Default,,0000,0000,0000,,Instead of staining all of the cells inside of a tissue, Dialogue: 0,0:01:25.66,0:01:28.69,Default,,0000,0000,0000,,it somehow only stains about one percent of them. Dialogue: 0,0:01:28.69,0:01:32.03,Default,,0000,0000,0000,,It clears the forest, reveals the trees inside. Dialogue: 0,0:01:32.03,0:01:34.70,Default,,0000,0000,0000,,If everything had been labeled, nothing would have been visible. Dialogue: 0,0:01:34.70,0:01:36.75,Default,,0000,0000,0000,,So somehow it shows what's there. Dialogue: 0,0:01:36.75,0:01:39.42,Default,,0000,0000,0000,,Spanish neuroanatomist Santiago Ramon y Cajal, Dialogue: 0,0:01:39.42,0:01:42.26,Default,,0000,0000,0000,,who's widely considered the father of modern neuroscience, Dialogue: 0,0:01:42.26,0:01:46.16,Default,,0000,0000,0000,,applied this Golgi stain, which yields data which looks like this, Dialogue: 0,0:01:46.16,0:01:49.92,Default,,0000,0000,0000,,and really gave us the modern notion of the nerve cell, the neuron. Dialogue: 0,0:01:49.92,0:01:52.53,Default,,0000,0000,0000,,And if you're thinking of the brain as a computer, Dialogue: 0,0:01:52.53,0:01:54.54,Default,,0000,0000,0000,,this is the transistor. Dialogue: 0,0:01:54.54,0:01:56.62,Default,,0000,0000,0000,,And very quickly Cajal realized Dialogue: 0,0:01:56.62,0:01:58.95,Default,,0000,0000,0000,,that neurons don't operate alone, Dialogue: 0,0:01:58.95,0:02:00.79,Default,,0000,0000,0000,,but rather make connections with others Dialogue: 0,0:02:00.79,0:02:03.30,Default,,0000,0000,0000,,that form circuits just like in a computer. Dialogue: 0,0:02:03.30,0:02:06.69,Default,,0000,0000,0000,,Today, a century later, when researchers want to visualize neurons, Dialogue: 0,0:02:06.69,0:02:09.46,Default,,0000,0000,0000,,they light them up from the inside rather than darkening them. Dialogue: 0,0:02:09.46,0:02:10.61,Default,,0000,0000,0000,,And there's several ways of doing this. Dialogue: 0,0:02:10.61,0:02:12.33,Default,,0000,0000,0000,,But one of the most popular ones Dialogue: 0,0:02:12.33,0:02:14.42,Default,,0000,0000,0000,,involves green fluorescent protein. Dialogue: 0,0:02:14.42,0:02:16.08,Default,,0000,0000,0000,,Now green fluorescent protein, Dialogue: 0,0:02:16.08,0:02:19.23,Default,,0000,0000,0000,,which oddly enough comes from a bioluminescent jellyfish, Dialogue: 0,0:02:19.23,0:02:20.47,Default,,0000,0000,0000,,is very useful. Dialogue: 0,0:02:20.47,0:02:23.10,Default,,0000,0000,0000,,Because if you can get the gene for green fluorescent protein Dialogue: 0,0:02:23.10,0:02:24.78,Default,,0000,0000,0000,,and deliver it to a cell, Dialogue: 0,0:02:24.78,0:02:26.53,Default,,0000,0000,0000,,that cell will glow green -- Dialogue: 0,0:02:26.53,0:02:30.27,Default,,0000,0000,0000,,or any of the many variants now of green fluorescent protein, Dialogue: 0,0:02:30.27,0:02:31.94,Default,,0000,0000,0000,,you get a cell to glow many different colors. Dialogue: 0,0:02:31.94,0:02:33.46,Default,,0000,0000,0000,,And so coming back to the brain, Dialogue: 0,0:02:33.46,0:02:37.26,Default,,0000,0000,0000,,this is from a genetically engineered mouse called "Brainbow." Dialogue: 0,0:02:37.26,0:02:38.81,Default,,0000,0000,0000,,And it's so called, of course, Dialogue: 0,0:02:38.81,0:02:42.42,Default,,0000,0000,0000,,because all of these neurons are glowing different colors. Dialogue: 0,0:02:42.42,0:02:45.87,Default,,0000,0000,0000,,Now sometimes neuroscientists need to identify Dialogue: 0,0:02:45.87,0:02:48.92,Default,,0000,0000,0000,,individual molecular components of neurons, molecules, Dialogue: 0,0:02:48.92,0:02:50.71,Default,,0000,0000,0000,,rather than the entire cell. Dialogue: 0,0:02:50.71,0:02:52.42,Default,,0000,0000,0000,,And there's several ways of doing this, Dialogue: 0,0:02:52.42,0:02:53.89,Default,,0000,0000,0000,,but one of the most popular ones Dialogue: 0,0:02:53.89,0:02:56.08,Default,,0000,0000,0000,,involves using antibodies. Dialogue: 0,0:02:56.08,0:02:57.42,Default,,0000,0000,0000,,And you're familiar, of course, Dialogue: 0,0:02:57.42,0:03:00.37,Default,,0000,0000,0000,,with antibodies as the henchmen of the immune system. Dialogue: 0,0:03:00.37,0:03:02.79,Default,,0000,0000,0000,,But it turns out that they're so useful to the immune system Dialogue: 0,0:03:02.79,0:03:05.34,Default,,0000,0000,0000,,because they can recognize specific molecules, Dialogue: 0,0:03:05.34,0:03:07.46,Default,,0000,0000,0000,,like, for example, the coat protein Dialogue: 0,0:03:07.46,0:03:09.85,Default,,0000,0000,0000,,of a virus that's invading the body. Dialogue: 0,0:03:09.85,0:03:11.89,Default,,0000,0000,0000,,And researchers have used this fact Dialogue: 0,0:03:11.89,0:03:16.22,Default,,0000,0000,0000,,in order to recognize specific molecules inside of the brain, Dialogue: 0,0:03:16.22,0:03:18.86,Default,,0000,0000,0000,,recognize specific substructures of the cell Dialogue: 0,0:03:18.86,0:03:21.10,Default,,0000,0000,0000,,and identify them individually. Dialogue: 0,0:03:21.10,0:03:24.12,Default,,0000,0000,0000,,And a lot of the images I've been showing you here are very beautiful, Dialogue: 0,0:03:24.12,0:03:26.03,Default,,0000,0000,0000,,but they're also very powerful. Dialogue: 0,0:03:26.03,0:03:27.67,Default,,0000,0000,0000,,They have great explanatory power. Dialogue: 0,0:03:27.67,0:03:29.76,Default,,0000,0000,0000,,This, for example, is an antibody staining Dialogue: 0,0:03:29.76,0:03:33.28,Default,,0000,0000,0000,,against serotonin transporters in a slice of mouse brain. Dialogue: 0,0:03:33.28,0:03:34.96,Default,,0000,0000,0000,,And you've heard of serotonin, of course, Dialogue: 0,0:03:34.96,0:03:37.78,Default,,0000,0000,0000,,in the context of diseases like depression and anxiety. Dialogue: 0,0:03:37.78,0:03:39.19,Default,,0000,0000,0000,,You've heard of SSRIs, Dialogue: 0,0:03:39.19,0:03:42.09,Default,,0000,0000,0000,,which are drugs that are used to treat these diseases. Dialogue: 0,0:03:42.09,0:03:44.98,Default,,0000,0000,0000,,And in order to understand how serotonin works, Dialogue: 0,0:03:44.98,0:03:48.06,Default,,0000,0000,0000,,it's critical to understand where the serontonin machinery is. Dialogue: 0,0:03:48.06,0:03:49.65,Default,,0000,0000,0000,,And antibody stainings like this one Dialogue: 0,0:03:49.65,0:03:53.20,Default,,0000,0000,0000,,can be used to understand that sort of question. Dialogue: 0,0:03:53.20,0:03:55.76,Default,,0000,0000,0000,,I'd like to leave you with the following thought: Dialogue: 0,0:03:55.76,0:03:58.37,Default,,0000,0000,0000,,Green fluorescent protein and antibodies Dialogue: 0,0:03:58.37,0:04:01.37,Default,,0000,0000,0000,,are both totally natural products at the get-go. Dialogue: 0,0:04:01.37,0:04:04.15,Default,,0000,0000,0000,,They were evolved by nature Dialogue: 0,0:04:04.15,0:04:06.72,Default,,0000,0000,0000,,in order to get a jellyfish to glow green for whatever reason, Dialogue: 0,0:04:06.72,0:04:11.10,Default,,0000,0000,0000,,or in order to detect the coat protein of an invading virus, for example. Dialogue: 0,0:04:11.10,0:04:14.12,Default,,0000,0000,0000,,And only much later did scientists come onto the scene Dialogue: 0,0:04:14.12,0:04:16.14,Default,,0000,0000,0000,,and say, "Hey, these are tools, Dialogue: 0,0:04:16.14,0:04:18.26,Default,,0000,0000,0000,,these are functions that we could use Dialogue: 0,0:04:18.26,0:04:20.26,Default,,0000,0000,0000,,in our own research tool palette." Dialogue: 0,0:04:20.26,0:04:23.89,Default,,0000,0000,0000,,And instead of applying feeble human minds Dialogue: 0,0:04:23.89,0:04:25.78,Default,,0000,0000,0000,,to designing these tools from scratch, Dialogue: 0,0:04:25.78,0:04:28.68,Default,,0000,0000,0000,,there were these ready-made solutions right out there in nature Dialogue: 0,0:04:28.68,0:04:31.92,Default,,0000,0000,0000,,developed and refined steadily for millions of years Dialogue: 0,0:04:31.92,0:04:33.62,Default,,0000,0000,0000,,by the greatest engineer of all. Dialogue: 0,0:04:33.62,0:04:34.88,Default,,0000,0000,0000,,Thank you. Dialogue: 0,0:04:34.88,0:04:37.42,Default,,0000,0000,0000,,(Applause)