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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Snapshots of Life: Color Coding the Hippocampus

Hippocampus

Credit: Raunak Basu, University of Utah, Salt Lake City

The final frontier? Trekkies would probably say it’s space, but mapping the brain—the most complicated biological structure in the known universe—is turning out to be an amazing adventure in its own right. Not only are researchers getting better at charting the brain’s densely packed and varied cellular topography, they are starting to identify the molecules that neurons use to connect into the distinct information-processing circuits that allow all walks of life to think and experience the world.

This image shows distinct neural connections in a cross section of a mouse’s hippocampus, a region of the brain involved in the memory of facts and events. The large, crescent-shaped area in green is hippocampal zone CA1. Its highly specialized neurons, called place cells, serve as the brain’s GPS system to track location. It appears green because these neurons express cadherin-10. This protein serves as a kind of molecular glue that likely imparts specific functional properties to this region. [1]

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How Sleep Resets the Brain

dendrites

Caption: Colorized 3D reconstruction of dendrites. Neurons receive input from other neurons through synapses, most of which are located along the dendrites on tiny projections called spines.
Credit: The Center for Sleep and Consciousness, University of Wisconsin-Madison School of Medicine

People spend about a third of their lives asleep. When we get too little shut-eye, it takes a toll on attention, learning and memory, not to mention our physical health. Virtually all animals with complex brains seem to have this same need for sleep. But exactly what is it about sleep that’s so essential?

Two NIH-funded studies in mice now offer a possible answer. The two research teams used entirely different approaches to reach the same conclusion: the brain’s neural connections grow stronger during waking hours, but scale back during snooze time. This sleep-related phenomenon apparently keeps neural circuits from overloading, ensuring that mice (and, quite likely humans) awaken with brains that are refreshed and ready to tackle new challenges.

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Talking Music and Science with Yo-Yo Ma

It’s not every day that an amateur guitar picker gets to play a duet with an internationally renowned classical cellist. But that was my thrill this week as I joined Yo-Yo Ma in a creative interpretation of the traditional song, “How Can I Keep from Singing?” Our short jam session capped off Mr. Ma’s appearance as this year’s J. Edward Rall Cultural Lecture.

The event, which counts The Dalai Lama, Maya Angelou, and Atul Gawande among its distinguished alumni, this year took the form of a conversation on the intersection of music and science—and earned a standing ovation from a packed house of researchers, patients, and staff here on the National Institutes of Health (NIH) campus in Bethesda, MD.

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Creative Minds: Reverse Engineering Vision

Networks of neurons in the mouse retina

Caption: Networks of neurons in the mouse retina. Green cells form a special electrically coupled network; red cells express a distinctive fluorescent marker to distinguish them from other cells; blue cells are tagged with an antibody against an enzyme that makes nitric oxide, important in retinal signaling. Such images help to identify retinal cell types, their signaling molecules, and their patterns of connectivity.
Credit: Jason Jacoby and Gregory Schwartz, Northwestern University

For Gregory Schwartz, working in total darkness has its benefits. Only in the pitch black can Schwartz isolate resting neurons from the eye’s retina and stimulate them with their natural input—light—to get them to fire electrical signals. Such signals not only provide a readout of the intrinsic properties of each neuron, but information that enables the vision researcher to deduce how it functions and forges connections with other neurons.

The retina is the light-sensitive neural tissue that lines the back of the eye. Although only about the size of a postage stamp, each of our retinas contains an estimated 130 million cells and more than 100 distinct cell types. These cells are organized into multiple information-processing layers that work together to absorb light and translate it into electrical signals that stream via the optic nerve to the appropriate visual center in the brain. Like other parts of the eye, the retina can break down, and retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, continue to be leading causes of vision loss and blindness worldwide.

In his lab at Northwestern University’s Feinberg School of Medicine, Chicago, Schwartz performs basic research that is part of a much larger effort among vision researchers to assemble a parts list that accounts for all of the cell types needed to make a retina. Once Schwartz and others get closer to wrapping up this list, the next step will be to work out the details of the internal wiring of the retina to understand better how it generates visual signals. It’s the kind of information that holds the key for detecting retinal diseases earlier and more precisely, fixing miswired circuits that affect vision, and perhaps even one day creating an improved prosthetic retina.

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