Neuroscience

Astrocytes are brain cells that, among other things, help neurons form active connections with each other. The exact mechanism behind this process has been a mystery. Scientists in Nicola Allen’s lab have begun to uncover more about these important cells. Allen and first author Isabella Farhy-Tselnicker discovered that astrocytes initiate communication between pairs of neurons by prompting specific changes in neurons through a protein called glypican 4. This protein influences both sending and receiving neurons, helping them make synaptic connections. It may be a target for better understanding neurodevelopmental disorders, such as autism, ADHD and schizophrenia, all of which may result at least partially from faulty communication between neurons. The work was published in Neuron on October 11, 2017.

Sensory neurons regulate how we recognize touch and pain as well as body movement and position, but neuroscientists are only now beginning to unravel this circuitry. New research from Kuo-Fen Lee’s lab, co–first authored by Zhijiang Lee and Christopher Donnelly, and in collaboration with researchers at the University of Michigan, shows how a protein involved in many different signaling pathways plays a key role in pain signaling in the brain. This “busybody” protein, called p75, enhances the survival of proteins that support sensory neurons involved in transmitting pain signals. When p75 is removed, the survival-promoting signal of these proteins is reduced and the neurons that respond to this signal gradually degenerate. These findings could lead to new insights into neurological disorders, as well as spinal cord injuries and other traumas. The work was published on October 17, 2017, in Cell Reports.

Every day, websites and apps crunch huge sets of information to find data points that resemble each other, such as products that are similar to past purchases. These tasks are called similarity searches, and performing them well—and fast—has been an ongoing challenge for computer scientists. Salk faculty Saket Navlakha and Charles Stevens, together with collaborator Sanjoy Dasgupta of UC San Diego, have shown that fruit fly brains, in their efforts to identify similar odors, may have found a better way to perform similarity searches. Current computer algorithms find similar items by reducing the amount of information associated with each item. Fly brains do the opposite, expanding the amount of information associated with each item, which allows them to better distinguish similar from dissimilar. When the researchers applied this approach of expanding rather than reducing information associated with data to three standard datasets, they found the fly method dramatically improved search performance. They reported their findings in Science on November 9, 2017.

We think the brain masterminds our actions, but a surprising amount of movement-related information is processed in the spinal cord. When we move, motor circuits in the spinal cord are constantly barraged by information from sensory receptors in the skin and muscles, information as varied as what our limbs are doing or what the ground underfoot feels like. This information is critical for actions like walking or standing still. Researchers in Martyn Goulding’s lab have solved a long-standing mystery about how spinal cords know when to pay attention to certain pieces of information and when to ignore them. Goulding, first author Stephanie Koch and others, in work published in Neuron on December 7, 2017, showed that specific neurons, called RORβ interneurons, inhibit the transmission of potentially disruptive sensory information during walking, allowing for a fluid gait.

The experimental drug J147, a synthetic, modified version of the curcumin molecule found in the spice turmeric, is almost ready for human trials. The lab of Dave Schubert developed J147 while looking for plant compounds that reverse cellular and molecular aging in the brain. Since then, the team has shown J147 reverses memory deficits, drives the production of new brain cells and slows or reverses Alzheimer’s disease progression in mice. Now Schubert, first author Josh Goldberg and their colleagues have figured out how J147 works: in a study published in Aging Cell on January 9, 2018, they reported that the drug binds to an enzyme called ATP synthase, which is found in our cells’ power-generating organelles (mitochondria). The team showed that, by manipulating ATP synthase activity, they could protect brain cells from multiple toxicities associated with aging. Unraveling J147’s mechanism of action is a critical step towards clinical trials in humans.