In June 2021, neuroscientists, researchers, collaborators and others convened online to discuss and explore the latest neuroscience research. Several researchers funded by the National Science Foundation’s NeuroNex Program also participated in the meeting.
Here, we provide a compilation of NeuroNex-funded research that was presented at the conference.

How much do we truly understand about movement and balance? Researchers have done their best to build robots that can achieve the same level of balance control as animals, with some success. Until recently, that effort had been focused on the hindlimb. Now, researchers at Case Western Reserve University and Portland State University have built a biomechanical model of a rat with a focus on the forelimb in hopes of better understanding how those muscles are engaged when the animal is moving. "The biomechanical model of the rat will enable us to study theories of neural control in balance, standing, walking, and running, and provide guidance for building quadruped robots," says Portland State University's Joshua Mak.

"The biomechanical model of the rat will enable us to study theories of neural control in balance, standing, walking, and running, and provide guidance for building quadruped robots."

While technological advances in neuroscience have helped us better monitor and analyze brain activity during different kinds of behavior, efforts to describe that behavior have lagged, particularly because a single, formal framework to do so doesn't exist. As a solution, researchers at Washington University in St. Louis and Cold Spring Harbor Laboratory proposed a description language to "abstract and standardize behavioral task descriptions on two layers," as noted in the poster.

 

While we primarily think of birds as flight animals, they are, in fact, also skilled terrestrial bipeds, with a 230-million-year locomotor legacy inherited from non-flying theropod dinosaurs. Consider the quail: This ground bird is an exceptional bipedal athlete with robust movement strategies that keep it safe from falls, collisions, and other injuries. Researchers at Friedrich-Schiller-University Jena in Germany and Northwestern University are exploring how the quail combines simple control rules, musculoskeletal mechanics and sensorimotor control to achieve agile and stable locomotion. "Neuromechanical principles for economical, agile and stable bipedal locomotion inform human and animal treatment of movement disorders, rehabilitation strategies, and bio-inspired robotics, and shed light on locomotion of extinct animals," says Friedrich-Schiller-University Jena's Emanuel Andrada.  

"Neuromechanical principles for economical, agile and stable bipedal locomotion inform human and animal treatment of movement disorders, rehabilitation strategies, bio-inspired robotics, and shed light on locomotion of extinct animals."

This is what 21st century research looks like: In an effort to better understand the role that our brains play in controlling movement, scientists at Portland State University have created a robot that has a 3D printed skeleton with artificial leg muscles. Researchers control the robot's muscles using a neural controller based on a model they developed of spinal and brain circuits. "This research is important because it allows us to investigate, using robots, the neural pathways that influence muscle control in human body movements," says Ben Bolen, PhD student at Portland State University's Department of Mechanical and Materials Engineering and contributor to the poster.          

 

Meet Muscle Mutt, a dog robot whose movement is controlled by a neural controller. Researchers rely on Muscle Mutt to better understand strategies employed by the nervous system to regulate walking. "Animals, even newborns, integrate more information and manipulate the environment in more complex ways than any robot currently made," says Fletcher Young, a Case Western Reserve University student involved in this research. "We believe that by controlling robots in the same way the animals control their bodies, we will be able to develop robots that are more lifelike, agile, and robust."

"We believe that by controlling robots in the same way the animals control their bodies, we will be able to develop robots that are more lifelike, agile, and robust."

How much input does the brain of a stick insect have when it comes to walking? In an effort to explore how the lower levels of the insect nervous system operate, researchers at West Virginia University and Case Western Reserve University created a biologically driven model of that lower section including a scaled-up robotic insect leg. They examined how different mechanisms could affect walkinginformation that will help explain how the brain and lower nervous system communicate to produce capable movement and, ultimately, provide inspiration for creating robot control software with some of the same capabilities.

Researchers have developed a modular model of the brain of the marine sea slug, Aplyisa californica in hopes of better understanding the biomechanics responsible for the slug's feeding behavior. The modular nature of the model allows researchers to test how adjusting the complexity of the brain model, biomechanics model, or muscle models affects a simulated behavior. "Our modular model of sea slug feeding will allow us to create more realistic models of the animal which we can use to understand how the brain and body work together to interact with the world," says Vickie Webster-Wood, assistant professor at Carnegie Mellon University and co-PI on the C3NS NeuroNex Network.

"Our modular model of sea slug feeding will allow us to create more realistic models of the animal which we can use to understand how the brain and body work together to interact with the world."

Nemonic, the NeuroNex hub based out of UC Santa Barbara, is focused on developing state-of-the-art technology for multiphoton imaging and related techniques and sharing it with the neuroscience community. While many imaging efforts require an animal to be asleep or unconscious, Nemonic is advancing technologies that enable multiphoton imaging and stimulation on animals that are awake. In addition, the team is developing imaging modalities that not only result in high-resolution images but can also use extended excitation sources while still being compatible with scattering specimens. 

Animals such as fireflies and jellyfish use a chemical reaction to create bioluminescent light. In the labs of the Bioluminescence Hub, researchers create molecular constructs where a BioLuminescent (BL) chemical reaction releases light that can be detected by a nearby OptoGenetic (OG) element. Using this BL-OG technique, researchers can control the activity of individual neurons or the connections between them. They can also use bioluminescent light as a visual indicator of calcium, a technique that has advantages over imaging with fluorescence.

 

What role do our nervous systems play as we move, communicate, and interact with our surroundings? That's the focus of the NeuroNex Network, Communication, Coordination, and Control in Neuromechanical Systems. Four interdisciplinary research groups from multiple US and international universities are collaborating to create a conceptual modeling framework that can predict control of differently sized organisms ranging from fruit flies to dogs. “Understanding how nervous systems control adaptive behavior like walking or feeding will provide new ways of thinking about control in both animals and robots," says Hillel Chiel, professor at Case Western Reserve University and co-principal investigator on the NeuroNex project.

"Understanding how nervous systems control adaptive behavior like walking or feeding will provide new ways of thinking about control in both animals and robots."

Researchers introduced the microLED optoelectrode where tiny LEDs were placed close to electrodes for enabling optical stimulation in small, targeted areas of the brain. Eusik Yoon, a professor at the University of Michigan, along with a team of collaborators extended the capability of the microLED optoelectrode to accommodate more than a hundred LEDs to precisely target neurons across a larger brain area. 

The best scientific breakthroughs come from collaborationwhether it's across disciplines, backgrounds, or skill levels. BRAIN initiative projects have taken concrete steps toward promoting high levels of inclusion such as expanding research partnerships, training and recruiting aspiring scientists, and instilling an interest in science among young kids. “By focusing efforts on novel technologies and innovation to tackle as yet unsolvable challenges, the BRAIN initiative has evolved into an infrastructure that enables transcending barriers including institutional affiliation and membership in underrepresented groups," says Ute Hochgeschwender, a neuroscience professor at Central Michigan University and a key member of the BRAIN Initiative.

"By focusing efforts on novel technologies and innovation to tackle as yet unsolvable challenges, the BRAIN initiative has evolved into an infrastructure that enables transcending barriers including institutional affiliation and membership in underrepresented groups."

From a stick insect to an elephant, animals control their muscles in order to walk. But what role does the size of an animal play in movement? Research out of Case Western Reserve University and Portland State University has shown that while larger animals activate their leg muscles in short bursts, relying on the weight of their limbs to do much of the work, small animals with lighter limbs must use their muscles for longer periods of time. "Since most of the building blocks of the nervous system are the same regardless of size, we are interested in learning about how the nervous system controls its muscles when animals are big or small," says Fletcher Young, Case Western Reserve University student.

"We are interested in learning about how the nervous system controls its muscles when animals are big or small."

All animals appear to move in more or less the same way, however, the forces that muscles must exert to move vary between animals. Researchers recently estimated how the properties of an animal's body might differ between differently sized animals, then calculated the forces required to move the body at different speeds. They found surprising similarities and differences between all kinds of animals, based only on the animal's size and how fast it moved. "Better understanding how different animals move enables us to compare the control strategies used by the very different animals that our Network studies: the fruit fly, sea slug, and rat," says Nicholas Szczecinski, an assistant professor at West Virginia University. "If these diverse animals control their motions in the same way, that would suggest fundamental principles of motion and control that can be applied in other contexts, for example, when designing mobile robots, studying human motor pathologies, or controlling powered protheses used by human patients."

"If these diverse animals control their motions in the same way, that would suggest fundamental principles of motion and control that can be applied in other contexts, for example, when designing mobile robots, studying human motor pathologies, or controlling powered protheses used by human patients."

Researchers at Case Western Reserve University and Portland State University are examining the rhythmic pattern of a neural model and its response to disturbance. This neural model could serve as a crucial component in any simulation model or robot. "Such analysis will benefit the design and implementation of future models investigating locomotion control," says Kaiyu Deng of Case Western Reserve University.

Three-photon excitation microscopy has double-to-triple the penetration depth in biological tissue over two-photon imaging. The laser technology used for generating high-energy pulses used for three-photon excitation is relatively new and the repetition rates of the laser sources are typically low at approximately 1–2 MHz. As a result, pulse shape distortions and pulse-to-pulse variability can markedly impact image quality. The Nemonic Hub has implemented state-of-the-art pulse measurements and developed new techniques for examining the performance of lasers used in three-photon microscopy. Researchers then demonstrated how these techniques can be used to provide precise measurements of pulse shape, pulse energy and pulse-to-pulse intensity variability, all of which ultimately impact imaging.

The ability to generate and sustain mental representations, independent of sensory experience or motor actions, is the foundation of abstract thought. An international group of scientists is examining the neural basis of this fundamental operation, and how it expands over primate brain evolution. They are finding unique molecular, cellular and circuit properties that allow recently evolved circuits to represent information without the need for sensory stimulation. 

Even animals like sea slugs can change their behavior when necessary. If an animal encounters tough seaweed, or loses contact with it, it has to change its behavior quickly. To learn more, researchers have created a model of both the feeding muscles and the neural control in the marine sea slug Aplysia californica that runs very quickly and can change behavior depending on whether or not it senses seaweed, and how hard it is to swallow that seaweed. "The model we created provides a way of understanding how they do this, which could lead to new ways of manipulating the nervous system, and might even lead to new controllers for soft robots," says Vickie Webster-Wood, assistant professor at Carnegie Mellon University and co-PI on the C3NS NeuroNex Network.

Yusaku Hontani, a postdoctoral researcher at Cornell University, discusses the challenges related to 3-photon microscopy (3PM) including an oftentimes weak fluorescence signal as well as the difficulty of carrying out multi-color 3PM imaging. As a solution, Hontani and a team of researchers developed a new 3PM excitation system that explores excitation to a higher-energy state. "In neuroscience (and in life science in general), observation of cell-cell interactions in living animals is essential," says Hontani. "3P microscopy enables deep-tissue observation in intact animal brains, but two different lasers were needed to do multi-color 3P imaging, which complicate the setup and cause more heat damage. Our new method enables multi-color imaging using single laser, which needs no complication of the 3P microscopy setup and induces no additional heat damage."

"Our new method enables multi-color imaging using single laser, which needs no complication of the 3P microscopy setup and induces no additional heat damage."

When it comes to studying movement, researchers need a highly accurate view of bones, joints, and muscles. While x-ray cameras help provide 3D positions of several of these parts under the surface of the skin, the process to annotate them is still manual, laborious, and expensive. As a solution, researchers tapped into a neural-network based markerless tracking software that can automatically estimate the position of features on the surface of the skin, and trained it to use X-ray data and live videos to get data on features and parts under the skin. Thus, says Diya Basrai of Northwestern University, "with just a couple of video cameras, labs without access to expensive high-speed X-ray acquisition technology can use this technique to quantify the movement in skeletal structure of an animal undergoing a behavior." 

"With just a couple of video cameras, labs without access to expensive high-speed X-ray acquisition technology can use this technique to quantify the movement in skeletal structure of an animal undergoing a behavior."

As part of this NeuroNex project, researchers dig deeper into the synapses or connections between billions of neurons in the brain that form neural circuits. While these circuits are key to guiding much of our behaviorallowing us to think, feel, and rememberthere's a lot to be learned about synaptic weight and its role in shaping neural circuits. "It is a thrill to have an international team of experts approaching the question to define synaptic weight from molecules to connectomes with integration across these levels of analysis," says Kristen Harris, a neuroscience professor at the University of Texas-Austin and Principal Investigator on the NeuroNex Project, Enabling Identification and Impact of Synaptic Weight in Functional Networks. "Having a whole team that serves to coordinate the tools that make this possible has also been deeply rewarding. We look forward to making an efficient pipeline for theses analyses in the future."

"It is a thrill to have an international team of experts approaching the question to define synaptic weight from molecules to connectomes with integration across these levels of analysis."

Researchers at Howard Hughes Medical Institute and the University of Cologne, Germany, have joined forces to identify interneurons in the nervous system of a fruit fly that transmit information from the ventral nerve cord in the thorax to the brain. As part of this effort, the researchers have developed methodological approaches that allow for the identification of more than 100 interneurons.          

How the structure of neural networks is shaped by experiences, and, in turn, determines their function is a central question in neuroscience. A team at the University of Houston has developed computational and theoretical tools that allow them to uncover the interactions between cells that form neural networks from data, explain how those interactions change due to experiences, and understand how the resulting connectivity and function are related.

The Nemonic Hub has developed an imaging systemSPatIal Frequency modulation Imaging or SPIFIthat employs two stages of modulation. The first stage is the Wavelength Domain and the second is the Spatial Domain. By operating both stages synchronously, researchers can implement linear excitation, two-dimensional, and single element detection imaging with enhanced resolution capability. 

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