The Cajal exhibit of drawings was here in Vancouver (Canada) this last fall (2017) and I still carry the memory of that glorious experience (see my Sept. 11, 2017 posting for more about the show and associated events). It seems Cajal’s drawings had a similar response in New York city, from a January 18, 2018 article by Roberta Smith for the New York Times,
Explorations led by local and Spanish scientists, artists, and entrepreneurs who will share their unique perspectives on particular aspects of the exhibition. (2:00 pm on select Tuesdays and Saturdays)
Tue, May 8 – Mark Harnett, Fred and Carole Middleton Career Development Professor at MIT and McGovern Institute Investigator Sat, May 26 – Marion Boulicault, MIT Graduate Student and Neuroethics Fellow in the Center for Sensorimotor Neural Engineering Tue, June 5 – Kelsey Allen, Graduate researcher, MIT Center for Brains, Minds, and Machines Sat, Jun 23 – Francisco Martin-Martinez, Research Scientist in MIT’s Laboratory for Atomistic & Molecular Mechanics and President of the Spanish Foundation for Science and Technology Jul 21 – Alex Gomez-Marin, Principal Investigator of the Behavior of Organisms Laboratory in the Instituto de Neurociencias, Spain Tue, Jul 31– Julie Pryor, Director of Communications at the McGovern Institute for Brain Research at MIT Tue, Aug 28 – Satrajit Ghosh, Principal Research Scientist at the McGovern Institute for Brain Research at MIT, Assistant Professor in the Department of Otolaryngology at Harvard Medical School, and faculty member in the Speech and Hearing Biosciences and Technology program in the Harvard Division of Medical Sciences
Drop in and explore expansion microscopy in our maker-space.
Visualizing Science Workshop
Experiential learning with micro-scale biological images. (pre-registration required)
Researchers share the latest on neural anatomy, signal transmission, and modern imaging techniques.
Teen Science Café: Mindful Matters
MIT researchers studying the brain share their mind-blowing findings.
Neuron Paint Night
Create a painting of cerebral cortex neurons and learn about the EyeWire citizen science game.
Cerebral Cinema Series
Hear from researchers and then compare real science to depictions on the big screen.
Test your brain power in a night of science trivia and short, snappy research talks.
Come back to see our exciting lineup for the fall!
If you don’t have a chance to see the show or if you’d like a preview, I encourage you to read Smith’s article as it has embedded several Cajal drawings and rendered them exceptionally well.
Drawing of the cells of the chick cerebellum by Santiago Ramón y Cajal, from “Estructura de los centros nerviosos de las aves,” Madrid, circa 1905
Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries.
His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks.
As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species?
At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron—one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the “butterflies of the soul.”
Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism and intellectual disability.
Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out.
Now, in a study published in the March 22  issue of Nature, researchers from Harvard Medical School, New York Genome Center, New York University and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.
Using single-cell analysis—a technology that allows scientists to track cellular behavior one cell at a time—the team traced the lineage of interneurons from their earliest precursor states to their mature forms in mice. The researchers identified key genetic programs that determine the fate of developing interneurons, as well as when these programs are switched on or off.
The findings serve as a guide for efforts to shed light on interneuron function and may help inform new treatment strategies for disorders involving their dysfunction, the authors said.
“We knew more than 100 years ago that this huge diversity of morphologically interesting cells existed in the brain, but their specific individual roles in brain function are still largely unclear,” said co-senior author Gordon Fishell, HMS professor of neurobiology and a faculty member at the Stanley Center for Psychiatric Research at the Broad.
“Our study provides a road map for understanding how and when distinct interneuron subtypes develop, giving us unprecedented insight into the biology of these cells,” he said. “We can now investigate interneuron properties as they emerge, unlock how these important cells function and perhaps even intervene when they fail to develop correctly in neuropsychiatric disease.”
A hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative Commons
Origins and Fates
In collaboration with co-senior author Rahul Satija, core faculty member of the New York Genome Center, Fishell and colleagues analyzed brain regions in developing mice known to contain precursor cells that give rise to interneurons.
Using Drop-seq, a single-cell sequencing technique created by researchers at HMS and the Broad, the team profiled gene expression in thousands of individual cells at multiple time points.
This approach overcomes a major limitation in past research, which could analyze only the average activity of mixtures of many different cells.
In the current study, the team found that the precursor state of all interneurons had similar gene expression patterns despite originating in three separate brain regions and giving rise to 14 or more interneuron subtypes alone—a number still under debate as researchers learn more about these cells.
“Mature interneuron subtypes exhibit incredible diversity. Their morphology and patterns of connectivity and activity are so different from each other, but our results show that the first steps in their maturation are remarkably similar,” said Satija, who is also an assistant professor of biology at New York University.
“They share a common developmental trajectory at the earliest stages, but the seeds of what will cause them to diverge later—a handful of genes—are present from the beginning,” Satija said.
As they profiled cells at later stages in development, the team observed the initial emergence of four interneuron “cardinal” classes, which give rise to distinct fates. Cells were committed to these fates even in the early embryo. By developing a novel computational strategy to link precursors with adult subtypes, the researchers identified individual genes that were switched on and off when cells began to diversify.
For example, they found that the gene Mef2c—mutations of which are linked to Alzheimer’s disease, schizophrenia and neurodevelopmental disorders in humans—is an early embryonic marker for a specific interneuron subtype known as Pvalb neurons. When they deleted Mef2c in animal models, Pvalb neurons failed to develop.
These early genes likely orchestrate the execution of subsequent genetic subroutines, such as ones that guide interneuron subtypes as they migrate to different locations in the brain and ones that help form unique connection patterns with other neural cell types, the authors said.
The identification of these genes and their temporal activity now provide researchers with specific targets to investigate the precise functions of interneurons, as well as how neurons diversify in general, according to the authors.
“One of the goals of this project was to address an incredibly fascinating developmental biology question, which is how individual progenitor cells decide between different neuronal fates,” Satija said. “In addition to these early markers of interneuron divergence, we found numerous additional genes that increase in expression, many dramatically, at later time points.”
The association of some of these genes with neuropsychiatric diseases promises to provide a better understanding of these disorders and the development of therapeutic strategies to treat them, a particularly important notion given the paucity of new treatments, the authors said.
Over the past 50 years, there have been no fundamentally new classes of neuropsychiatric drugs, only newer versions of old drugs, the researchers pointed out.
“Our repertoire is no better than it was in the 1970s,” Fishell said.
“Neuropsychiatric diseases likely reflect the dysfunction of very specific cell types. Our study puts forward a clear picture of what cells to look at as we work to shed light on the mechanisms that underlie these disorders,” Fishell said. “What we will find remains to be seen, but we have new, strong hypotheses that we can now test.”
As a resource for the research community, the study data and software are open-source and freely accessible online.
A gallery of the drawings of Santiago Ramón y Cajal is currently on display in New York City, and will open at the MIT Museum in Boston in May 2018.
Christian Mayer, Christoph Hafemeister and Rachel Bandler served as co-lead authors on the study.
This work was supported by the National Institutes of Health (R01 NS074972, R01 NS081297, MH071679-12, DP2-HG-009623, F30MH114462, T32GM007308, F31NS103398), the European Molecular Biology Organization, the National Science Foundation and the Simons Foundation.
This paper is behind a paywall.