Creative Minds: Seeing Memories in a New Light

Steve Ramirez

Steve Ramirez/Joshua Sariñana

Whether it’s lacing up for a morning run, eating blueberry scones, or cheering on the New England Patriots, Steve Ramirez loves life and just about everything in it. As an undergraduate at Boston University, this joie de vivre actually made Ramirez anxious about choosing just one major. A serendipitous conversation helped him realize that all of the amazing man-made stuff in our world has a common source: the human brain.

So, Ramirez decided to pursue neuroscience and began exploring the nature of memory. Employing optogenetics (using light to control brain cells) in mice, he tagged specific neurons that housed fear-inducing memories, making the neurons light sensitive and amenable to being switched on at will.

In groundbreaking studies that earned him a spot in Forbes 2015 “30 Under 30” list, Ramirez showed that it’s possible to reactivate memories experimentally in a new context, recasting them in either a more negative or positive behavior-changing light [1–3]. Now, with support from a 2016 NIH Director’s Early Independence Award, Ramirez, who runs his own lab at Boston University, will explore whether activating good memories holds promise for alleviating chronic stress and psychiatric disease.

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Creative Minds: Mapping the Biocircuitry of Schizophrenia and Bipolar Disorder

Bruce Yankner

Bruce Yankner

As a graduate student in the 1980s, Bruce Yankner wondered what if cancer-causing genes switched on in non-dividing neurons of the brain. Rather than form a tumor, would those genes cause neurons to degenerate? To explore such what-ifs, Yankner spent his days tinkering with neural cells, using viruses to insert various mutant genes and study their effects. In a stroke of luck, one of Yankner’s insertions encoded a precursor to a protein called amyloid. Those experiments and later ones from Yankner’s own lab showed definitively that high concentrations of amyloid, as found in the brains of people with Alzheimer’s disease, are toxic to neural cells [1].

The discovery set Yankner on a career path to study normal changes in the aging human brain and their connection to neurodegenerative diseases. At Harvard Medical School, Boston, Yankner and his colleague George Church are now recipients of an NIH Director’s 2016 Transformative Research Award to apply what they’ve learned about the aging brain to study changes in the brains of younger people with schizophrenia and bipolar disorder, two poorly understood psychiatric disorders.

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NIH Family Members Giving Back: Kafui Dzirasa

Kafui Dzirasa at UMBC

Caption: Kafui Dzirasa (front center) with the current group of Meyerhoff Scholars at University of Maryland, Baltimore County.
Credit: Olubukola Abiona

Kafui Dzirasa keeps an open-door policy in his busy NIH-supported lab at Duke University, Durham, NC. If his trainees have a quick question or just need to discuss an upcoming experiment, they’re always welcome to pull up a chair. The donuts are on him.

But when trainees pop by his office and see he’s out for the day, they have a good idea of what it means. Dzirasa has most likely traveled up to his native Maryland to volunteer as a mentor for students in a college program that will be forever near and dear to him. It’s the Meyerhoff Scholars Program at the University of Maryland, Baltimore County (UMBC). Since its launch in 1988, this groundbreaking program has served as a needed pipeline to help increase diversity in the sciences—with more than 1,000 alumni, including Dzirasa, and 270 current students of all races.

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Creative Minds: A Transcriptional “Periodic Table” of Human Neurons

neuronal cell

Caption: Mouse fibroblasts converted into induced neuronal cells, showing neuronal appendages (red), nuclei (blue) and the neural protein tau (yellow).
Credit: Kristin Baldwin, Scripps Research Institute, La Jolla, CA

Writers have The Elements of Style, chemists have the periodic table, and biomedical researchers could soon have a comprehensive reference on how to make neurons in a dish. Kristin Baldwin of the Scripps Research Institute, La Jolla, CA, has received a 2016 NIH Director’s Pioneer Award to begin drafting an online resource that will provide other researchers the information they need to reprogram mature human skin cells reproducibly into a variety of neurons that closely resemble those found in the brain and nervous system.

These lab-grown neurons could be used to improve our understanding of basic human biology and to develop better models for studying Alzheimer’s disease, autism, and a wide range of other neurological conditions. Such questions have been extremely difficult to explore in mice and other animal models because they have shorter lifespans and different brain structures than humans.

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Fighting Depression: Ketamine Metabolite May Offer Benefits Without the Risks

Depressed Woman

Thinkstock/Ryan McVay

For people struggling with severe depression, antidepressants have the potential to provide much-needed relief, but they often take weeks to work. That’s why there is growing excitement about reports that the anesthetic drug ketamine, when delivered intravenously in very low doses, can lift depression and suicidal thoughts within a matter of hours. Still, there has been reluctance to consider ketamine for widespread treatment of depression because, even at low doses, it can produce very distressing side effects, such as dissociation—a sense of disconnection from one’s own thoughts, feelings, and sense of identity. Now, new findings suggest there may be a way to tap into ketamine’s depression-fighting benefits without the side effects.

In a mouse study published in the journal Nature, an NIH-funded research team found that the antidepressant effects of ketamine are produced not by the drug itself, but by one of its metabolites—a substance formed as the body breaks ketamine down. What’s more, the work demonstrates that this beneficial metabolite does not cause the risky dissociation effects associated with ketamine. While further development and subsequent clinical trials are needed, the findings are a promising step toward the development of a new generation of rapid-acting antidepressant drugs.

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