{"id":172969,"date":"2015-10-12T20:00:30","date_gmt":"2015-10-13T00:00:30","guid":{"rendered":"http:\/\/webadmin.news-harvard.go-vip.net\/gazette\/gazette\/?p=172969"},"modified":"2015-10-12T20:00:30","modified_gmt":"2015-10-13T00:00:30","slug":"closer-view-of-the-brain","status":"publish","type":"post","link":"https:\/\/news.harvard.edu\/gazette\/story\/2015\/10\/closer-view-of-the-brain\/","title":{"rendered":"Closer view of the brain"},"content":{"rendered":"<header\n\tclass=\"wp-block-harvard-gazette-article-header alignfull article-header is-style-square has-light-background has-colored-heading\"\n\tstyle=\" \"\n>\n\t\n\t<div class=\"article-header__content\">\n\t\t\t<a\n\t\t\tclass=\"article-header__category\"\n\t\t\thref=\"https:\/\/news.harvard.edu\/gazette\/section\/health\/\"\n\t\t>\n\t\t\tHealth\t\t<\/a>\n\t\t\n\t\t<h1 class=\"article-header__title wp-block-heading has-large-text\">\n\t\tCloser view of the brain\t<\/h1>\n\n\t\n\t\n\t<div class=\"article-header__meta\">\n\t\t<div class=\"wp-block-post-author\">\n\t\t\t<address class=\"wp-block-post-author__content\">\n\t\t\t\t\t<p class=\"author wp-block-post-author__name\">\n\t\tPeter Reuell\t<\/p>\n\t\t\t<p class=\"wp-block-post-author__byline\">\n\t\t\tHarvard Staff Writer\t\t<\/p>\n\t\t\t\t\t<\/address>\n\t\t<\/div>\n\n\t\t<time class=\"article-header__date\" datetime=\"2015-10-12\">\n\t\t\tOctober 12, 2015\t\t<\/time>\n\n\t\t<span class=\"article-header__reading-time\">\n\t\t\t5 min read\t\t<\/span>\n\t<\/div>\n\n\t\t\t<\/div>\n\t\t\n\t\t\t<h2 class=\"article-header__subheading wp-block-heading\">\n\t\t\tBreakthrough in imaging for Lichtman and colleagues \t\t<\/h2>\n\t\t\n<\/header>\n\n\n\n<div class=\"wp-block-group alignwide has-global-padding is-content-justification-center is-layout-constrained wp-block-group-is-layout-constrained\">\n\n\n\t\t<p>For Harvard neurobiologist Jeff Lichtman, the question hasn\u2019t been whether scientists will ever understand the brain, but how closely they\u2019ll have to look before they do.<\/p>\n<p>The answer, it turns out, is very, very close.<\/p>\n<p>Led by Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ram\u00f3n y Cajal Professor of Arts and Sciences, a team of researchers has succeeded in comprehensively imaging \u2014 at the nano scale \u2014 a small portion of mouse brain. What they found, Lichtman said, could open the door to understanding how learning alters the brain.<\/p>\n<p>A team of scientists from universities including Harvard, Johns Hopkins, and MIT contributed to the research by helping build the imaging acquisition and analysis pipeline required to study the brain in such detail. The co-authors are Narayanan Kasthuri, Kenneth Hayworth, Daniel Berger, Richard Schalek, Jos\u00e9 Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio V\u00e1zquez-Reina, Verena Kaynig, Thouis Jones, Mike Roberts, Josh Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Vogelstein, Randal Burns, Daniel Sussman, Carey Priebe, and Hanspeter Pfister.<\/p>\n\r\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<span class=\"embed-youtube\" style=\"text-align:center; display: block;\"><iframe loading=\"lazy\" class=\"youtube-player\" width=\"640\" height=\"360\" src=\"https:\/\/www.youtube.com\/embed\/nEOpUypJgyw?version=3&#038;rel=1&#038;showsearch=0&#038;showinfo=1&#038;iv_load_policy=1&#038;fs=1&#038;hl=en-US&#038;autohide=2&#038;wmode=transparent\" allowfullscreen=\"true\" style=\"border:0;\" sandbox=\"allow-scripts allow-same-origin allow-popups allow-presentation allow-popups-to-escape-sandbox\"><\/iframe><\/span>\n<\/div>\n<figcaption class=\"wp-element-caption\">Harvard University&#8217;s Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell<\/figcaption><\/figure>\n\n\r\n\n<p>\u201cOne thing that surprised us was \u2026 that axons often made two, three, or even more synapses on the same dendrite,\u201d Lichtman said. \u201cThe understanding had been that dendritic spines are there to collect information from as many different axons as possible, yet we found many cases where the same axon found different spines on the same dendrite.<\/p>\n<p>\u201cThat was interesting because it suggests those multiple-contact axons are communicating more powerfully with the dendrite because they have more connections with it,\u201d he continued. \u201cWhen we looked closely, we found that it\u2019s not possible for this result to happen by chance \u2014 some axons preferred to form synapses on some nearby dendrites more than they did with other equally nearby dendrites. That says that even in this trivially small volume, we are already beginning to see that the brain\u2019s wiring diagram is organized in some interesting ways. It is not simply that nerve cells establish random contacts with nearby neurons, as was expected. There\u2019s something purposeful going on here.\u201d<\/p>\n<p>The study also suggested that dendritic spines are not shaped by axons\u2019 electrical activity, contrary to wide belief.<\/p>\n<p>\u201cThe shape of spines goes from long and skinny to very short and stubby,\u201d Lichtman said. \u201cIt\u2019s thought that electrical activity, based on the axon, should generate that shape, but because we had multiple spines with different shapes enervated by the same axon, we know they have the same electrical activity.\u201d<\/p>\n<p>For Lichtman and his colleagues, the study is the culmination of years of effort, not only to understand the brain, but also to develop systems for collecting precise images of how the brain is wired.<\/p>\n<p>\u201cIt\u2019s a very, very tall staircase that we are trying to climb, but at least we\u2019re on the staircase,\u201d Lichtman said.<\/p>\n<p>Getting to step one was a yearlong process.<\/p>\n<p>\u201cThis paper took somewhere between five and six years to complete,\u201d Lichtman said. \u201cMuch of that time was devoted to inventing the pipeline we use to capture these images. That required developing a means of cutting brain very thin, collecting the brain sections, and using this tape-based method that had not been used previously.\u201d<\/p>\n<p>With the system in place, Lichtman and colleagues set about using electron microscopes to capture images of tissue and shaping a method to trace cells through the various layers, allowing researchers to reconstruct axons, dendrites, and synapses into 3-D images. The images were also used to build a database that was mined for insights into neuron connectivity.<\/p>\n<p>\u201cWhat this paper describes is the pipeline where we start with a physical piece of brain and end up at the other end with a digital brain,\u201d Lichtman said. \u201cIt\u2019s been digitized and is minable, so you can look at this digital brain sample over and over again without having to dissect a real brain for each new question.\u201d<\/p>\n<p>The important insights in the study required a surprisingly small amount of brain.<\/p>\n<p>\u201cWe imaged a section of brain that was 40-by-40-by-40 microns, and in that volume we completely saturated and reconstructed an area that was only 1,500 cubic microns,\u201d Lichtman said. \u201cIt\u2019s about three-billionths the size of a mouse brain, so it\u2019s very small, but you have to start somewhere.\u201d<\/p>\n<p>The selected region centers on a few dendritic processes of two large brain cells, allowing researchers to get a sense of just how many other nerve cells are located in the immediate vicinity of one small segment of a few neurons.<\/p>\n<p>What they discovered came as a surprise even to Lichtman.<\/p>\n<p>\u201cWe found 1,500 nerve cells provide nerve cell axons and dendrites in this little volume, which is a shockingly large number,\u201d he said. \u201cThose nerve cells contribute to a lot of other areas as well, but that gives you some sense of the extraordinary networking in the brains of mammals.\u201d<\/p>\n<p>In fact, connections in the brain are so densely packed, state-of-the-art imaging can only begin to scratch the surface.<\/p>\n<p>\u201cWe found a synapse approximately every cubic micron,\u201d Lichtman said. \u201cThat means if you look at images of the brain captured using high-resolution techniques like functional magnetic resonance imaging, where the pixel size represents one cubic millimeter, then there are one billion synapses within every pixel.\u201d<\/p>\n<p>It may be there, in that staggering density, he said, that the study\u2019s final message lies.<\/p>\n<p>\u201cIt\u2019s very hard to get a complete feeling for this,\u201d Lichtman said. \u201cThere is this na\u00efve view that if you just know a little bit more, then understanding it will be easier, but in this case, knowing a little more has shown us how much further we have to go before we\u2019ll understand brains.\u201d<\/p>\n<p>The study was described in a July 30 paper in the journal Cell.<\/p>\n\n\n\n<\/div>\n\n\t\t","protected":false},"excerpt":{"rendered":"<p>A team of researchers has succeeded in imaging \u2014 at the nano scale \u2014 every item in a small portion of mouse brain. What they found, Lichtman said, could open the door to, among other things, understanding how learning alters the brain.<\/p>\n","protected":false},"author":105622744,"featured_media":172990,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"gz_ga_pageviews":11,"gz_ga_lastupdated":"2018-12-20 04:09","document_color_palette":null,"author":"Peter Reuell","affiliation":"Harvard Staff Writer","_category_override":"","_yoast_wpseo_primary_category":"","_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[39644],"tags":[5180,7439,10568,10571,17706,19015,21424,24384,25442,27327,32959],"gazette-formats":[],"series":[],"class_list":["post-172969","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","tag-axon","tag-cell","tag-dendrite","tag-dendritic-spine","tag-imaging","tag-jeff-lichtman","tag-learning","tag-molecular-and-cellular-biology","tag-neuron","tag-peter-reuell","tag-synapse"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v23.0 (Yoast SEO v27.1.1) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Closer view of the brain &#8212; Harvard Gazette<\/title>\n<meta name=\"description\" content=\"A team of researchers has succeeded in imaging \u2014 at the nano scale \u2014 every item in a small portion of mouse brain. 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biology\",\"neuron\",\"peter reuell\",\"synapse\"],\"dateCreated\":\"2015-10-13T00:00:30Z\",\"datePublished\":\"2015-10-13T00:00:30Z\",\"dateModified\":\"2015-10-13T00:00:30Z\"}<\/script>","tracker_url":"https:\/\/cdn.parsely.com\/keys\/news.harvard.edu\/p.js"},"jetpack_featured_media_url":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/08\/brainwired_605.jpg","has_blocks":true,"block_data":{"0":{"blockName":"harvard-gazette\/article-header","attrs":{"blockColorPalette":"","coloredHeading":"","creditText":"","displayDetails":"","displayTitle":"","categoryId":39644,"mediaAlt":"","mediaCaption":"","mediaId":"","mediaSize":"","mediaType":"","mediaUrl":"","poster":"","title":"Closer view of the brain","subheading":"Breakthrough in imaging for Lichtman and colleagues ","className":"is-style-square","backgroundFixed":false,"backgroundTone":"light","centeredImage":false,"coloredBackground":false,"displayOverlay":true,"fadeInText":false,"isAmbient":false,"mediaHeight":0,"mediaLength":"","mediaPosition":"","mediaWidth":0,"posterText":"","titleAbove":false,"useUncroppedImage":false,"lock":[],"metadata":[]},"innerBlocks":[],"innerHTML":"","innerContent":[],"rendered":"<header\n\tclass=\"wp-block-harvard-gazette-article-header alignfull article-header is-style-square has-light-background has-colored-heading\"\n\tstyle=\" \"\n>\n\t\n\t<div class=\"article-header__content\">\n\t\t\t<a\n\t\t\tclass=\"article-header__category\"\n\t\t\thref=\"https:\/\/news.harvard.edu\/gazette\/section\/health\/\"\n\t\t>\n\t\t\tHealth\t\t<\/a>\n\t\t\n\t\t<h1 class=\"article-header__title wp-block-heading has-large-text\">\n\t\tCloser view of the brain\t<\/h1>\n\n\t\n\t\n\t<div class=\"article-header__meta\">\n\t\t<div class=\"wp-block-post-author\">\n\t\t\t<address class=\"wp-block-post-author__content\">\n\t\t\t\t\t<p class=\"author wp-block-post-author__name\">\n\t\tPeter Reuell\t<\/p>\n\t\t\t<p class=\"wp-block-post-author__byline\">\n\t\t\tHarvard Staff Writer\t\t<\/p>\n\t\t\t\t\t<\/address>\n\t\t<\/div>\n\n\t\t<time class=\"article-header__date\" datetime=\"2015-10-12\">\n\t\t\tOctober 12, 2015\t\t<\/time>\n\n\t\t<span class=\"article-header__reading-time\">\n\t\t\t5 min read\t\t<\/span>\n\t<\/div>\n\n\t\t\t<\/div>\n\t\t\n\t\t\t<h2 class=\"article-header__subheading wp-block-heading\">\n\t\t\tBreakthrough in imaging for Lichtman and colleagues \t\t<\/h2>\n\t\t\n<\/header>\n"},"2":{"blockName":"core\/group","attrs":{"templateLock":false,"metadata":{"name":"Article content"},"align":"wide","layout":{"type":"constrained","justifyContent":"center"},"tagName":"div","lock":[],"className":"","style":[],"backgroundColor":"","textColor":"","gradient":"","fontSize":"","fontFamily":"","borderColor":"","ariaLabel":"","anchor":""},"innerBlocks":[{"blockName":"core\/freeform","attrs":{"content":"","lock":[],"metadata":[]},"innerBlocks":[],"innerHTML":"\n\t\t<p>For Harvard neurobiologist Jeff Lichtman, the question hasn\u2019t been whether scientists will ever understand the brain, but how closely they\u2019ll have to look before they do.<\/p>\n<p>The answer, it turns out, is very, very close.<\/p>\n<p>Led by Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ram\u00f3n y Cajal Professor of Arts and Sciences, a team of researchers has succeeded in comprehensively imaging \u2014 at the nano scale \u2014 a small portion of mouse brain. What they found, Lichtman said, could open the door to understanding how learning alters the brain.<\/p>\n<p>A team of scientists from universities including Harvard, Johns Hopkins, and MIT contributed to the research by helping build the imaging acquisition and analysis pipeline required to study the brain in such detail. The co-authors are Narayanan Kasthuri, Kenneth Hayworth, Daniel Berger, Richard Schalek, Jos\u00e9 Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio V\u00e1zquez-Reina, Verena Kaynig, Thouis Jones, Mike Roberts, Josh Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Vogelstein, Randal Burns, Daniel Sussman, Carey Priebe, and Hanspeter Pfister.<\/p>\n","innerContent":["\n\t\t<p>For Harvard neurobiologist Jeff Lichtman, the question hasn\u2019t been whether scientists will ever understand the brain, but how closely they\u2019ll have to look before they do.<\/p>\n<p>The answer, it turns out, is very, very close.<\/p>\n<p>Led by Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ram\u00f3n y Cajal Professor of Arts and Sciences, a team of researchers has succeeded in comprehensively imaging \u2014 at the nano scale \u2014 a small portion of mouse brain. What they found, Lichtman said, could open the door to understanding how learning alters the brain.<\/p>\n<p>A team of scientists from universities including Harvard, Johns Hopkins, and MIT contributed to the research by helping build the imaging acquisition and analysis pipeline required to study the brain in such detail. The co-authors are Narayanan Kasthuri, Kenneth Hayworth, Daniel Berger, Richard Schalek, Jos\u00e9 Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio V\u00e1zquez-Reina, Verena Kaynig, Thouis Jones, Mike Roberts, Josh Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Vogelstein, Randal Burns, Daniel Sussman, Carey Priebe, and Hanspeter Pfister.<\/p>\n"],"rendered":"\n\t\t<p>For Harvard neurobiologist Jeff Lichtman, the question hasn\u2019t been whether scientists will ever understand the brain, but how closely they\u2019ll have to look before they do.<\/p>\n<p>The answer, it turns out, is very, very close.<\/p>\n<p>Led by Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ram\u00f3n y Cajal Professor of Arts and Sciences, a team of researchers has succeeded in comprehensively imaging \u2014 at the nano scale \u2014 a small portion of mouse brain. What they found, Lichtman said, could open the door to understanding how learning alters the brain.<\/p>\n<p>A team of scientists from universities including Harvard, Johns Hopkins, and MIT contributed to the research by helping build the imaging acquisition and analysis pipeline required to study the brain in such detail. The co-authors are Narayanan Kasthuri, Kenneth Hayworth, Daniel Berger, Richard Schalek, Jos\u00e9 Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio V\u00e1zquez-Reina, Verena Kaynig, Thouis Jones, Mike Roberts, Josh Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Vogelstein, Randal Burns, Daniel Sussman, Carey Priebe, and Hanspeter Pfister.<\/p>\n"},{"blockName":"core\/embed","attrs":{"url":"https:\/\/www.youtube.com\/watch?v=nEOpUypJgyw","type":"video","responsive":true,"providerNameSlug":"youtube","className":"wp-embed-aspect-16-9 wp-has-aspect-ratio","caption":"Harvard University's Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell","allowResponsive":true,"previewable":true,"lock":[],"metadata":[],"align":"","style":[]},"innerBlocks":[],"innerHTML":"\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\nhttps:\/\/www.youtube.com\/watch?v=nEOpUypJgyw\n<\/div>\n<figcaption class=\"wp-element-caption\">Harvard University's Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell<\/figcaption><\/figure>\n","innerContent":["\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\nhttps:\/\/www.youtube.com\/watch?v=nEOpUypJgyw\n<\/div>\n<figcaption class=\"wp-element-caption\">Harvard University's Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell<\/figcaption><\/figure>\n"],"rendered":"\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\nhttps:\/\/www.youtube.com\/watch?v=nEOpUypJgyw\n<\/div>\n<figcaption class=\"wp-element-caption\">Harvard University's Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell<\/figcaption><\/figure>\n"},{"blockName":"core\/freeform","attrs":{"content":"","lock":[],"metadata":[]},"innerBlocks":[],"innerHTML":"\n<p>\u201cOne thing that surprised us was \u2026 that axons often made two, three, or even more synapses on the same dendrite,\u201d Lichtman said. \u201cThe understanding had been that dendritic spines are there to collect information from as many different axons as possible, yet we found many cases where the same axon found different spines on the same dendrite.<\/p>\n<p>\u201cThat was interesting because it suggests those multiple-contact axons are communicating more powerfully with the dendrite because they have more connections with it,\u201d he continued. \u201cWhen we looked closely, we found that it\u2019s not possible for this result to happen by chance \u2014 some axons preferred to form synapses on some nearby dendrites more than they did with other equally nearby dendrites. That says that even in this trivially small volume, we are already beginning to see that the brain\u2019s wiring diagram is organized in some interesting ways. It is not simply that nerve cells establish random contacts with nearby neurons, as was expected. There\u2019s something purposeful going on here.\u201d<\/p>\n<p>The study also suggested that dendritic spines are not shaped by axons\u2019 electrical activity, contrary to wide belief.<\/p>\n<p>\u201cThe shape of spines goes from long and skinny to very short and stubby,\u201d Lichtman said. \u201cIt\u2019s thought that electrical activity, based on the axon, should generate that shape, but because we had multiple spines with different shapes enervated by the same axon, we know they have the same electrical activity.\u201d<\/p>\n<p>For Lichtman and his colleagues, the study is the culmination of years of effort, not only to understand the brain, but also to develop systems for collecting precise images of how the brain is wired.<\/p>\n<p>\u201cIt\u2019s a very, very tall staircase that we are trying to climb, but at least we\u2019re on the staircase,\u201d Lichtman said.<\/p>\n<p>Getting to step one was a yearlong process.<\/p>\n<p>\u201cThis paper took somewhere between five and six years to complete,\u201d Lichtman said. \u201cMuch of that time was devoted to inventing the pipeline we use to capture these images. That required developing a means of cutting brain very thin, collecting the brain sections, and using this tape-based method that had not been used previously.\u201d<\/p>\n<p>With the system in place, Lichtman and colleagues set about using electron microscopes to capture images of tissue and shaping a method to trace cells through the various layers, allowing researchers to reconstruct axons, dendrites, and synapses into 3-D images. The images were also used to build a database that was mined for insights into neuron connectivity.<\/p>\n<p>\u201cWhat this paper describes is the pipeline where we start with a physical piece of brain and end up at the other end with a digital brain,\u201d Lichtman said. \u201cIt\u2019s been digitized and is minable, so you can look at this digital brain sample over and over again without having to dissect a real brain for each new question.\u201d<\/p>\n<p>The important insights in the study required a surprisingly small amount of brain.<\/p>\n<p>\u201cWe imaged a section of brain that was 40-by-40-by-40 microns, and in that volume we completely saturated and reconstructed an area that was only 1,500 cubic microns,\u201d Lichtman said. \u201cIt\u2019s about three-billionths the size of a mouse brain, so it\u2019s very small, but you have to start somewhere.\u201d<\/p>\n<p>The selected region centers on a few dendritic processes of two large brain cells, allowing researchers to get a sense of just how many other nerve cells are located in the immediate vicinity of one small segment of a few neurons.<\/p>\n<p>What they discovered came as a surprise even to Lichtman.<\/p>\n<p>\u201cWe found 1,500 nerve cells provide nerve cell axons and dendrites in this little volume, which is a shockingly large number,\u201d he said. \u201cThose nerve cells contribute to a lot of other areas as well, but that gives you some sense of the extraordinary networking in the brains of mammals.\u201d<\/p>\n<p>In fact, connections in the brain are so densely packed, state-of-the-art imaging can only begin to scratch the surface.<\/p>\n<p>\u201cWe found a synapse approximately every cubic micron,\u201d Lichtman said. \u201cThat means if you look at images of the brain captured using high-resolution techniques like functional magnetic resonance imaging, where the pixel size represents one cubic millimeter, then there are one billion synapses within every pixel.\u201d<\/p>\n<p>It may be there, in that staggering density, he said, that the study\u2019s final message lies.<\/p>\n<p>\u201cIt\u2019s very hard to get a complete feeling for this,\u201d Lichtman said. \u201cThere is this na\u00efve view that if you just know a little bit more, then understanding it will be easier, but in this case, knowing a little more has shown us how much further we have to go before we\u2019ll understand brains.\u201d<\/p>\n<p>The study was described in a July 30 paper in the journal Cell.<\/p>\n\n","innerContent":["\n<p>\u201cOne thing that surprised us was \u2026 that axons often made two, three, or even more synapses on the same dendrite,\u201d Lichtman said. \u201cThe understanding had been that dendritic spines are there to collect information from as many different axons as possible, yet we found many cases where the same axon found different spines on the same dendrite.<\/p>\n<p>\u201cThat was interesting because it suggests those multiple-contact axons are communicating more powerfully with the dendrite because they have more connections with it,\u201d he continued. \u201cWhen we looked closely, we found that it\u2019s not possible for this result to happen by chance \u2014 some axons preferred to form synapses on some nearby dendrites more than they did with other equally nearby dendrites. That says that even in this trivially small volume, we are already beginning to see that the brain\u2019s wiring diagram is organized in some interesting ways. It is not simply that nerve cells establish random contacts with nearby neurons, as was expected. There\u2019s something purposeful going on here.\u201d<\/p>\n<p>The study also suggested that dendritic spines are not shaped by axons\u2019 electrical activity, contrary to wide belief.<\/p>\n<p>\u201cThe shape of spines goes from long and skinny to very short and stubby,\u201d Lichtman said. \u201cIt\u2019s thought that electrical activity, based on the axon, should generate that shape, but because we had multiple spines with different shapes enervated by the same axon, we know they have the same electrical activity.\u201d<\/p>\n<p>For Lichtman and his colleagues, the study is the culmination of years of effort, not only to understand the brain, but also to develop systems for collecting precise images of how the brain is wired.<\/p>\n<p>\u201cIt\u2019s a very, very tall staircase that we are trying to climb, but at least we\u2019re on the staircase,\u201d Lichtman said.<\/p>\n<p>Getting to step one was a yearlong process.<\/p>\n<p>\u201cThis paper took somewhere between five and six years to complete,\u201d Lichtman said. \u201cMuch of that time was devoted to inventing the pipeline we use to capture these images. That required developing a means of cutting brain very thin, collecting the brain sections, and using this tape-based method that had not been used previously.\u201d<\/p>\n<p>With the system in place, Lichtman and colleagues set about using electron microscopes to capture images of tissue and shaping a method to trace cells through the various layers, allowing researchers to reconstruct axons, dendrites, and synapses into 3-D images. The images were also used to build a database that was mined for insights into neuron connectivity.<\/p>\n<p>\u201cWhat this paper describes is the pipeline where we start with a physical piece of brain and end up at the other end with a digital brain,\u201d Lichtman said. \u201cIt\u2019s been digitized and is minable, so you can look at this digital brain sample over and over again without having to dissect a real brain for each new question.\u201d<\/p>\n<p>The important insights in the study required a surprisingly small amount of brain.<\/p>\n<p>\u201cWe imaged a section of brain that was 40-by-40-by-40 microns, and in that volume we completely saturated and reconstructed an area that was only 1,500 cubic microns,\u201d Lichtman said. \u201cIt\u2019s about three-billionths the size of a mouse brain, so it\u2019s very small, but you have to start somewhere.\u201d<\/p>\n<p>The selected region centers on a few dendritic processes of two large brain cells, allowing researchers to get a sense of just how many other nerve cells are located in the immediate vicinity of one small segment of a few neurons.<\/p>\n<p>What they discovered came as a surprise even to Lichtman.<\/p>\n<p>\u201cWe found 1,500 nerve cells provide nerve cell axons and dendrites in this little volume, which is a shockingly large number,\u201d he said. \u201cThose nerve cells contribute to a lot of other areas as well, but that gives you some sense of the extraordinary networking in the brains of mammals.\u201d<\/p>\n<p>In fact, connections in the brain are so densely packed, state-of-the-art imaging can only begin to scratch the surface.<\/p>\n<p>\u201cWe found a synapse approximately every cubic micron,\u201d Lichtman said. \u201cThat means if you look at images of the brain captured using high-resolution techniques like functional magnetic resonance imaging, where the pixel size represents one cubic millimeter, then there are one billion synapses within every pixel.\u201d<\/p>\n<p>It may be there, in that staggering density, he said, that the study\u2019s final message lies.<\/p>\n<p>\u201cIt\u2019s very hard to get a complete feeling for this,\u201d Lichtman said. \u201cThere is this na\u00efve view that if you just know a little bit more, then understanding it will be easier, but in this case, knowing a little more has shown us how much further we have to go before we\u2019ll understand brains.\u201d<\/p>\n<p>The study was described in a July 30 paper in the journal Cell.<\/p>\n\n"],"rendered":"\n<p>\u201cOne thing that surprised us was \u2026 that axons often made two, three, or even more synapses on the same dendrite,\u201d Lichtman said. \u201cThe understanding had been that dendritic spines are there to collect information from as many different axons as possible, yet we found many cases where the same axon found different spines on the same dendrite.<\/p>\n<p>\u201cThat was interesting because it suggests those multiple-contact axons are communicating more powerfully with the dendrite because they have more connections with it,\u201d he continued. \u201cWhen we looked closely, we found that it\u2019s not possible for this result to happen by chance \u2014 some axons preferred to form synapses on some nearby dendrites more than they did with other equally nearby dendrites. That says that even in this trivially small volume, we are already beginning to see that the brain\u2019s wiring diagram is organized in some interesting ways. It is not simply that nerve cells establish random contacts with nearby neurons, as was expected. There\u2019s something purposeful going on here.\u201d<\/p>\n<p>The study also suggested that dendritic spines are not shaped by axons\u2019 electrical activity, contrary to wide belief.<\/p>\n<p>\u201cThe shape of spines goes from long and skinny to very short and stubby,\u201d Lichtman said. \u201cIt\u2019s thought that electrical activity, based on the axon, should generate that shape, but because we had multiple spines with different shapes enervated by the same axon, we know they have the same electrical activity.\u201d<\/p>\n<p>For Lichtman and his colleagues, the study is the culmination of years of effort, not only to understand the brain, but also to develop systems for collecting precise images of how the brain is wired.<\/p>\n<p>\u201cIt\u2019s a very, very tall staircase that we are trying to climb, but at least we\u2019re on the staircase,\u201d Lichtman said.<\/p>\n<p>Getting to step one was a yearlong process.<\/p>\n<p>\u201cThis paper took somewhere between five and six years to complete,\u201d Lichtman said. \u201cMuch of that time was devoted to inventing the pipeline we use to capture these images. That required developing a means of cutting brain very thin, collecting the brain sections, and using this tape-based method that had not been used previously.\u201d<\/p>\n<p>With the system in place, Lichtman and colleagues set about using electron microscopes to capture images of tissue and shaping a method to trace cells through the various layers, allowing researchers to reconstruct axons, dendrites, and synapses into 3-D images. The images were also used to build a database that was mined for insights into neuron connectivity.<\/p>\n<p>\u201cWhat this paper describes is the pipeline where we start with a physical piece of brain and end up at the other end with a digital brain,\u201d Lichtman said. \u201cIt\u2019s been digitized and is minable, so you can look at this digital brain sample over and over again without having to dissect a real brain for each new question.\u201d<\/p>\n<p>The important insights in the study required a surprisingly small amount of brain.<\/p>\n<p>\u201cWe imaged a section of brain that was 40-by-40-by-40 microns, and in that volume we completely saturated and reconstructed an area that was only 1,500 cubic microns,\u201d Lichtman said. \u201cIt\u2019s about three-billionths the size of a mouse brain, so it\u2019s very small, but you have to start somewhere.\u201d<\/p>\n<p>The selected region centers on a few dendritic processes of two large brain cells, allowing researchers to get a sense of just how many other nerve cells are located in the immediate vicinity of one small segment of a few neurons.<\/p>\n<p>What they discovered came as a surprise even to Lichtman.<\/p>\n<p>\u201cWe found 1,500 nerve cells provide nerve cell axons and dendrites in this little volume, which is a shockingly large number,\u201d he said. \u201cThose nerve cells contribute to a lot of other areas as well, but that gives you some sense of the extraordinary networking in the brains of mammals.\u201d<\/p>\n<p>In fact, connections in the brain are so densely packed, state-of-the-art imaging can only begin to scratch the surface.<\/p>\n<p>\u201cWe found a synapse approximately every cubic micron,\u201d Lichtman said. \u201cThat means if you look at images of the brain captured using high-resolution techniques like functional magnetic resonance imaging, where the pixel size represents one cubic millimeter, then there are one billion synapses within every pixel.\u201d<\/p>\n<p>It may be there, in that staggering density, he said, that the study\u2019s final message lies.<\/p>\n<p>\u201cIt\u2019s very hard to get a complete feeling for this,\u201d Lichtman said. \u201cThere is this na\u00efve view that if you just know a little bit more, then understanding it will be easier, but in this case, knowing a little more has shown us how much further we have to go before we\u2019ll understand brains.\u201d<\/p>\n<p>The study was described in a July 30 paper in the journal Cell.<\/p>\n\n"}],"innerHTML":"\n<div class=\"wp-block-group alignwide\">\n\n\r\n\n\r\n\n\n<\/div>\n","innerContent":["\n<div class=\"wp-block-group alignwide\">\n\n","\r\n","\n\r\n","\n\n<\/div>\n"],"rendered":"\n<div class=\"wp-block-group alignwide has-global-padding is-content-justification-center is-layout-constrained wp-block-group-is-layout-constrained\">\n\n\n\t\t<p>For Harvard neurobiologist Jeff Lichtman, the question hasn\u2019t been whether scientists will ever understand the brain, but how closely they\u2019ll have to look before they do.<\/p>\n<p>The answer, it turns out, is very, very close.<\/p>\n<p>Led by Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ram\u00f3n y Cajal Professor of Arts and Sciences, a team of researchers has succeeded in comprehensively imaging \u2014 at the nano scale \u2014 a small portion of mouse brain. What they found, Lichtman said, could open the door to understanding how learning alters the brain.<\/p>\n<p>A team of scientists from universities including Harvard, Johns Hopkins, and MIT contributed to the research by helping build the imaging acquisition and analysis pipeline required to study the brain in such detail. The co-authors are Narayanan Kasthuri, Kenneth Hayworth, Daniel Berger, Richard Schalek, Jos\u00e9 Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio V\u00e1zquez-Reina, Verena Kaynig, Thouis Jones, Mike Roberts, Josh Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Vogelstein, Randal Burns, Daniel Sussman, Carey Priebe, and Hanspeter Pfister.<\/p>\n\r\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\nhttps:\/\/www.youtube.com\/watch?v=nEOpUypJgyw\n<\/div>\n<figcaption class=\"wp-element-caption\">Harvard University's Jeff Lichtman and colleagues use automated EM technologies to probe the structures of neural tissue at nanometer resolution. Courtesy of Cell<\/figcaption><\/figure>\n\n\r\n\n<p>\u201cOne thing that surprised us was \u2026 that axons often made two, three, or even more synapses on the same dendrite,\u201d Lichtman said. \u201cThe understanding had been that dendritic spines are there to collect information from as many different axons as possible, yet we found many cases where the same axon found different spines on the same dendrite.<\/p>\n<p>\u201cThat was interesting because it suggests those multiple-contact axons are communicating more powerfully with the dendrite because they have more connections with it,\u201d he continued. \u201cWhen we looked closely, we found that it\u2019s not possible for this result to happen by chance \u2014 some axons preferred to form synapses on some nearby dendrites more than they did with other equally nearby dendrites. That says that even in this trivially small volume, we are already beginning to see that the brain\u2019s wiring diagram is organized in some interesting ways. It is not simply that nerve cells establish random contacts with nearby neurons, as was expected. There\u2019s something purposeful going on here.\u201d<\/p>\n<p>The study also suggested that dendritic spines are not shaped by axons\u2019 electrical activity, contrary to wide belief.<\/p>\n<p>\u201cThe shape of spines goes from long and skinny to very short and stubby,\u201d Lichtman said. \u201cIt\u2019s thought that electrical activity, based on the axon, should generate that shape, but because we had multiple spines with different shapes enervated by the same axon, we know they have the same electrical activity.\u201d<\/p>\n<p>For Lichtman and his colleagues, the study is the culmination of years of effort, not only to understand the brain, but also to develop systems for collecting precise images of how the brain is wired.<\/p>\n<p>\u201cIt\u2019s a very, very tall staircase that we are trying to climb, but at least we\u2019re on the staircase,\u201d Lichtman said.<\/p>\n<p>Getting to step one was a yearlong process.<\/p>\n<p>\u201cThis paper took somewhere between five and six years to complete,\u201d Lichtman said. \u201cMuch of that time was devoted to inventing the pipeline we use to capture these images. That required developing a means of cutting brain very thin, collecting the brain sections, and using this tape-based method that had not been used previously.\u201d<\/p>\n<p>With the system in place, Lichtman and colleagues set about using electron microscopes to capture images of tissue and shaping a method to trace cells through the various layers, allowing researchers to reconstruct axons, dendrites, and synapses into 3-D images. The images were also used to build a database that was mined for insights into neuron connectivity.<\/p>\n<p>\u201cWhat this paper describes is the pipeline where we start with a physical piece of brain and end up at the other end with a digital brain,\u201d Lichtman said. \u201cIt\u2019s been digitized and is minable, so you can look at this digital brain sample over and over again without having to dissect a real brain for each new question.\u201d<\/p>\n<p>The important insights in the study required a surprisingly small amount of brain.<\/p>\n<p>\u201cWe imaged a section of brain that was 40-by-40-by-40 microns, and in that volume we completely saturated and reconstructed an area that was only 1,500 cubic microns,\u201d Lichtman said. \u201cIt\u2019s about three-billionths the size of a mouse brain, so it\u2019s very small, but you have to start somewhere.\u201d<\/p>\n<p>The selected region centers on a few dendritic processes of two large brain cells, allowing researchers to get a sense of just how many other nerve cells are located in the immediate vicinity of one small segment of a few neurons.<\/p>\n<p>What they discovered came as a surprise even to Lichtman.<\/p>\n<p>\u201cWe found 1,500 nerve cells provide nerve cell axons and dendrites in this little volume, which is a shockingly large number,\u201d he said. \u201cThose nerve cells contribute to a lot of other areas as well, but that gives you some sense of the extraordinary networking in the brains of mammals.\u201d<\/p>\n<p>In fact, connections in the brain are so densely packed, state-of-the-art imaging can only begin to scratch the surface.<\/p>\n<p>\u201cWe found a synapse approximately every cubic micron,\u201d Lichtman said. \u201cThat means if you look at images of the brain captured using high-resolution techniques like functional magnetic resonance imaging, where the pixel size represents one cubic millimeter, then there are one billion synapses within every pixel.\u201d<\/p>\n<p>It may be there, in that staggering density, he said, that the study\u2019s final message lies.<\/p>\n<p>\u201cIt\u2019s very hard to get a complete feeling for this,\u201d Lichtman said. \u201cThere is this na\u00efve view that if you just know a little bit more, then understanding it will be easier, but in this case, knowing a little more has shown us how much further we have to go before we\u2019ll understand brains.\u201d<\/p>\n<p>The study was described in a July 30 paper in the journal Cell.<\/p>\n\n\n\n<\/div>\n"}},"jetpack-related-posts":[{"id":132231,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2013\/03\/first-santiago-ramon-y-cajal-professor-of-arts-and-sciences\/","url_meta":{"origin":172969,"position":0},"title":"First Santiago Ram\u00f3n y Cajal Professor is named","author":"harvardgazette","date":"March 11, 2013","format":false,"excerpt":"Jeff Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology, has been appointed as the first Ram\u00f3n y Cajal Professor of Arts and Sciences.","rel":"","context":"In &quot;Campus &amp; Community&quot;","block_context":{"text":"Campus &amp; Community","link":"https:\/\/news.harvard.edu\/gazette\/section\/campus-community\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/010613_litch_605m.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/010613_litch_605m.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/010613_litch_605m.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":383537,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2024\/04\/jeff-lichtman-named-dean-of-science\/","url_meta":{"origin":172969,"position":1},"title":"Jeff Lichtman named dean of science\u00a0","author":"harvardgazette","date":"April 30, 2024","format":false,"excerpt":"Neuroscientist inspired by \u2018great challenge\u2019 of leading life, physical sciences division in era of rapidly growing knowledge","rel":"","context":"In &quot;Campus &amp; Community&quot;","block_context":{"text":"Campus &amp; Community","link":"https:\/\/news.harvard.edu\/gazette\/section\/campus-community\/"},"img":{"alt_text":"Jeff Lichtman.","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2024\/04\/2500_Lichtman_020.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2024\/04\/2500_Lichtman_020.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2024\/04\/2500_Lichtman_020.jpg?resize=525%2C300 1.5x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2024\/04\/2500_Lichtman_020.jpg?resize=700%2C400 2x"},"classes":[]},{"id":138524,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2013\/05\/brainbow-version-2-0\/","url_meta":{"origin":172969,"position":2},"title":"\u2018Brainbow,\u2019 version 2.0","author":"harvardgazette","date":"May 15, 2013","format":false,"excerpt":"Led by Joshua Sanes and Jeff Lichtman, a group of Harvard researchers has made a host of technical improvements in the \u201cBrainbow\u201d imaging technique.","rel":"","context":"In &quot;Health&quot;","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/05\/brainbow_fig-3b_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/05\/brainbow_fig-3b_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/05\/brainbow_fig-3b_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":133907,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2013\/03\/a-look-inside-the-lab\/","url_meta":{"origin":172969,"position":3},"title":"A look inside the lab","author":"harvardgazette","date":"March 27, 2013","format":false,"excerpt":"The Faculty of Arts and Sciences\u2019 Division of Science recently relaunched its \u201cScience Research Lecture Series,\u201d aimed at introducing the broader local community to research conducted by Harvard faculty members. The talks will be held once a month in the Science Center, and will be open to the public.","rel":"","context":"In &quot;Campus &amp; Community&quot;","block_context":{"text":"Campus &amp; Community","link":"https:\/\/news.harvard.edu\/gazette\/section\/campus-community\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/042611_edwards_360_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/042611_edwards_360_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/03\/042611_edwards_360_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":364343,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2023\/09\/human-brain-too-big-to-map-so-theyre-starting-with-mice\/","url_meta":{"origin":172969,"position":4},"title":"Human brain seems impossible to map. What if we started with mice?","author":"gazettebeckycoleman","date":"September 26, 2023","format":false,"excerpt":"Harvard-led project seeks to create the first comprehensive diagram of every neural connection.","rel":"","context":"In &quot;Science &amp; Tech&quot;","block_context":{"text":"Science &amp; Tech","link":"https:\/\/news.harvard.edu\/gazette\/section\/science-technology\/"},"img":{"alt_text":"Microscopic image of brain with color-coded cells.","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2023\/09\/connectome-tall.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2023\/09\/connectome-tall.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2023\/09\/connectome-tall.jpg?resize=525%2C300 1.5x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2023\/09\/connectome-tall.jpg?resize=700%2C400 2x"},"classes":[]},{"id":165241,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2015\/01\/harvards-odyssey-unlocks-big-data\/","url_meta":{"origin":172969,"position":5},"title":"Harvard&#8217;s Odyssey unlocks big data","author":"harvardgazette","date":"January 26, 2015","format":false,"excerpt":"Harvard faculty and researchers are using big data to answer society\u2019s most challenging questions, and doing it with the help of FAS Research Computing (FASRC). Founded in 2007, FASRC had one goal: to provide Harvard faculty, students, and staff with leading-edge computational resources.","rel":"","context":"In &quot;Health&quot;","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/01\/fas-research-computing_still_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/01\/fas-research-computing_still_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/01\/fas-research-computing_still_605.jpg?resize=525%2C300 1.5x"},"classes":[]}],"jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts\/172969","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/users\/105622744"}],"replies":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/comments?post=172969"}],"version-history":[{"count":0,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts\/172969\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/media\/172990"}],"wp:attachment":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/media?parent=172969"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/categories?post=172969"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/tags?post=172969"},{"taxonomy":"format","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/gazette-formats?post=172969"},{"taxonomy":"series","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/series?post=172969"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}