An arrow points to patches of white mutant photoreceptor cells in the eyes of a grasshopper. Researchers on the NeuroNex project, Advancing neuronal and genetic approaches to animal behavior research, targeted the genes in those cells using CRISPR/Cas9 genome editing. Image credit: Dianne Duncan
The NeuroNex Project, Advancing neuronal and genetic approaches to animal behavior research, is focused on developing genetic tools to study the European honey bee and American grasshopper—both economically important insect species that currently lack the genetic and molecular technologies needed to study their physiology and behavior. As part of that effort, the team, led by PI Yehuda Ben-Shahar and Co-PI Barani Raman, is developing transgenic drivers—tools that will help manipulate gene expression in specific brain cells of the two species. They’re also trying to improve the way they insert new genes into the DNA of those organisms. However, as research goes, the team, based at Washington University in St. Louis, has had its fair share of challenges along the way such as figuring out how to efficiently produce and collect embryos, creating successful “markers” that let us see the changes they make, and identifying the specific parts of DNA that can report on neuronal activity. Another big challenge is that the genes controlling these insects are more complex and difficult to work with compared to the vinegar fly, which is commonly studied in similar projects. Despite these challenges, the NeuroNex team has been sharing their work with the public and other researchers, making their findings and tools available online via AddGene. They've been communicating with other groups that are also interested in these kinds of studies. They have also been invited to present their research in 2024 at the Royal Society’s Theo Murphy meetings series in London.
Mary Kate Joyce is a postdoctoral associate in the Department of Neuroscience at Yale University School of Medicine and part of the NeuroNex Project, The Fabric of the Primate Neocortex and the Origin of Mental Representations, where she’s doing comparative research between the prefrontal cortex of the macaque and marmoset, a smaller species of monkey. “This is an important question to pursue because marmosets are a great emerging and increasingly popular primate model,” says Joyce; they’re smaller, easier to handle, typically give birth to twins, and have shorter life spans—serving as a good intermediate for lab research between macaques and rodents. As part of this effort, Joyce relies on electron microscopy to look at how circuits in both species’ brains are organized as well as study the way receptors are distributed within their brain cells. She’s also studying key proteins critical in normal cognitive processes in macaques and mapping out similarities in the same region of the marmoset’s brain. “Doing all this comparative work at this stage is really important for us to understand how well the marmoset animal model fits some of the more complex functions associated with the prefrontal cortex and how well they model psychiatric disorders and neurological conditions that affect people.” Joyce has always had an interest in “what’s going wrong,” and as a neuroscientist, she says, “I love being part of the global effort to ameliorate the burden of psychiatric and mood disorders.” In fact, as part of the separate research effort, Joyce is also exploring the subcellular distribution of the brain's GluN2B receptors, in vulnerable prefrontal cortices, which have been found to play a part in emotion and mood regulation. As Joyce continues to tackle the numerous complexities that are part and parcel of neuroscience, she advises aspiring scientists to build an understanding of what you don’t know and can’t know. “This can really guide you in knowing what questions science can and can't answer.” And, she says, because neuroscience sits at the intersection of diverse scientific disciplines, there's an opportunity to think about a lot of big questions at once.
Researchers at Western University and the Salk Institute for Biological Studies in California have discovered yet another remarkable feature in the ever-complex brain: its ability to extrapolate information from an individual action and forecast subsequent related actions—essentially predicting the immediate future. When we see an object for instance, that information is received by the brain in waves that travel across interconnected neurons in a highly structured way, causing the brain to create a fuller picture of what’s occurring and what’s about to occur. They recently published their findings in Nature Communications. “We find that the connections between neurons in a single region of visual cortex can help to generate short-term predictions of incoming sensory input,” says senior author Lyle Muller, Assistant Professor at Western University’s Department of Applied Mathematics and Project Manager on the NeuroNex Project, The Fabric of the Primate Neocortex and the Origin of Mental Representations. “These connections generate complex activity patterns, layered on top of the input image, that appear to enable these short-term predictions.” By introducing a new network architecture and adapting a learning rule recently used to predict chaotic systems in physics, researchers trained networks to make short-term predictions of natural movie inputs. In the video above, we see a woman walking in “ground truth” (left panel). Based on the ground truth, the network can use its internal “recurrent” connections to predict the next course of action—the woman continuing to walk (second from left). Intriguingly, multiple versions of the walking legs are apparent in the internal dynamics of the network. These “ghost legs” may represent multiple potential predictions of future input, generated by the internal connections in the network, from which the network can then learn to select the correct prediction. The fourth panel on the right shows a static prediction that occurs when no internal recurrent connections are present, demonstrating that, in this model, the internal connections play an important role in creating dynamic short-term predictions of incoming inputs. While this is an early version of what’s to come, researchers can use this understanding of the brain to build similar predictive technologies and systems. “Understanding how the recurrent circuits of the visual cortex create short-term predictions can help us understand how our visual system processes the continuous stream of input from our eyes in real time,” says Muller. “These results could lead to new algorithms for processing and predicting movies in the future.”
NeuroNex brings together researchers working across disciplines into a coherent network to develop innovative, accessible, and shared technologies and approaches, as well as theoretical frameworks and computational modeling to advance understanding of brain function across organizational levels and a diversity of species.
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