Post by Former NIMH Director Thomas Insel: Neuroscience Advances Showcased in Washington
Anyone who wonders about the vitality of our field should have attended the Society for Neuroscience meeting here in Washington, DC, this week. Over 32,000 neuroscientists, many of them under 30, descended on Washington for five days of lectures, symposia, and posters about the nervous system. Having attended this meeting almost every year since 1982, this year I was struck by the increasing interest in neuropsychiatric disorders, especially autism and schizophrenia.
What was new this year? The connectome seemed to be everywhere. The connectome is the wiring diagram, the map of connections, of the brain. There were connectomes in nematodes, connectomes in mice, and connectomes in human brains. There were connectomes at the microscopic level, mapping every synapse; and connectomes at the macroscopic level, mapping fiber bundles in the brain. And just as the genome provided a consensus sequence that gave us an understanding of human genetic variation, the connectome may yield a map of individual variation in brain connections. Despite the importance of this information, wiring diagrams, like the original genome maps, are necessary but not sufficient for understanding how the brain works. In her plenary lecture, Cornelia Bargmann from Rockefeller University detailed factors that influence neural pathways—yielding different behaviors with the same underlying anatomy—in ways that are not evident from a wiring map.
As with the connectome, knowledge of the genome is only part of the puzzle of how genes shape development and behavior. Another topic that seemed to be everywhere was epigenetics—heritable differences in gene expression not the result of DNA sequence. Many presentations reported evidence of how experience may be encrypted in epigenetic changes that can be transmitted, and alter behavior, over generations. This work has important implications for understanding the complex interactions between environment and genes and the contributing roles of both in disorders of mental health.
Every year there is a hot new technique: Last year it was optogenetics, which uses light to turn on and turn off select neurons, providing the first precise method for manipulating brain circuits. This year there were hundreds of applications of this technique in rodents and monkeys, including selectively turning off a pathway between the prefrontal cortex and serotonin-producing cells to reduce depression-like behavior.
This year the new technique was induced pluripotent stem cells (iPScs). Skin cells taken from patients are treated to give them the capabilities of stem cells to divide and differentiate into any type of cell. These stem cells can then be grown in culture and induced to develop into a desired type of adult cell, for example, a neuron. Cardiac cells grown this way will begin to beat in the dish. Neurons and other brain cells are not quite so dramatic, but scientists at this meeting showed how cultured neurons derived from patients with neuropsychiatric disorders form abnormal connections and, amazingly, can be used to screen for new pharmacological treatments. Creating a “disease in a dish” may seem like science fiction (or science folly) for neuropsychiatric disorders, but this technique is already revolutionizing other areas of medicine and may be our best beachhead for investigating neurodevelopmental disorders associated with rare genetic mutations.
And on still another front, Dr. Huda Akil from the University of Michigan, reported on her group’s discovery of a family of growth factors involved in major depression, specifically a molecule called FGF2. In a completely unrelated study, Maha Elsayed and her colleagues at Yale reported the same molecule as an essential factor for antidepressant drug action.
But these findings barely scratch the surface of what has been an extraordinary week of exciting science on the brain and behavior. There should be little doubt that neuroscience has become the fundamental science of mental disorders. In spite of concerns about funding, the findings tell us that the field is thriving and, with continued support, our approach to mental illness will be transformed by neuroscience.