What motivates us to train for a marathon? How do we decide between chocolate cake and apple pie? And what role do our memories play in such choices? These inner workings of the brain have traditionally been difficult to study. The Simons Collaboration on the Global Brain (SCGB), launched in 2014, explores these questions by pairing new technologies for monitoring the brain with powerful computational and modeling techniques. The collaboration, led by David Tank of Princeton University and an executive committee, supports an interactive community of 73 scientists.
The SCGB was made possible by a recent technological revolution in neuroscience: For the first time in the field’s history, researchers can monitor the activity of thousands of neurons at single-cell resolution using various innovative sensors. These include high-density electrode arrays to track electrical changes and molecular tools to assay calcium concentration, an indirect measure of neuron activity. Scientists can also manipulate neuronal activity with optogenetics — a method by which neurons are genetically engineered so that they may be turned off and on with light — and then test the role those neurons play in cognition.
SCGB investigators are employing these tools to decipher the electrical and chemical activity of neural circuits and to examine how such neural codes — the language that neurons use to communicate — change over time to produce our thoughts and actions. They will explore how dynamic patterns of activity recall a memory, imagine the future or perform mental arithmetic. With the answers to these questions, neuroscientists can begin to build a mechanistic understanding of brain function.
Because the scientists also need new mathematical approaches to make sense of the huge volume of neural data being generated, the SCGB funds collaborations between experimentalists and theorists that combine the latest innovative technologies for recording and stimulating neural populations with the most powerful forms of analysis and modeling. “Investigators meet frequently to discuss experimental approaches, theory, models and computations that impact their individual projects. And they share data as it emerges,” a level of interaction that makes the SCGB distinct from other collaborations, says Gerald D. Fischbach, distinguished scientist and fellow at the foundation.
Today, the great majority of SCGB awards include two or more investigators, but a number of informal collaborations have emerged as well. SCGB investigators reported more than 50 newly formed collaborations last year, both within the SCGB and beyond. “The SCGB is a great catalyst for bringing together mathematicians and neuroscientists in a serious way — not just to hear each other talk,” says Markus Meister, a neuroscientist at the California Institute of Technology and SCGB investigator. “The individual projects are diverse, dealing with memory, decisions, judgments and other internal mental states, but they all share a common goal — to define algorithms by which populations of active nerve cells correspond to internal mental states,” says Fischbach.
For example, computational neuroscientist Shaul Druckmann and experimentalist Karel Svoboda, both from the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, are working to understand how the brain holds information, such as a phone number, in short-term memory. They discovered that the memory system is designed with redundancy in mind: Just as computers have backup memory systems, the brain appears to have a backup system for short-term memory.
Druckmann and Svoboda drew this conclusion by watching rodents trained to remember the location of an object for a short period. During the task, the scientists recorded neural activity in a brain region known as the premotor cortex, which spans both the left and right hemispheres of the brain. They found that if they briefly silenced the neural activity on just one side, the activity pattern tied to that memory quickly bounced back, undoing the temporary freeze and restoring activity to a pattern similar to that which occurs under normal conditions. However, if the scientists silenced both sides of the premotor cortex, or silenced only one side when the connection between hemispheres was severed, the memory was lost. The findings, published in Nature, suggest that neural activity in one hemisphere can act as a backup copy for short-term memory.
Even more significant was the discovery that the brain seems to select which neural activity to protect. The rodents’ brains restored only the activity pattern that was most tightly tied to the object’s location. Just as engineers build backup systems for the critical parts of a machine but not for the dispensable parts, the brain seems to ensure that the essential components of neural activity are resilient or resistant to damage. Druckmann says this is the most important outcome of the study. “It means that the concept of taking activity and decomposing it into important and non-important parts is not just something we as theoreticians like to do,” he says. “The brain also respects this principle — it doesn’t bother to correct the parts that aren’t important.”
The Druckmann and Svoboda labs are now extending the cutting-edge technology to silence neurons even more precisely. In future experiments, they hope to identify neural activity patterns relevant to short-term memory more specifically, and to determine whether changing those patterns alters behavior. “We want to push the patterns around a bit and see how they rearrange themselves,” Druckmann says.