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Discovery
NSF-funded researchers describe their cutting-edge brain research

Why and how are researchers studying the brains of mice, octopuses, zebra fish, frogs, lizards and cichlid fish?

Partha Mitra is contributing to the construction of the first 3-D map of the mouse brain.

Partha Mitra is contributing to the construction of the first 3-D map of the mouse brain.
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February 6, 2014

Our understanding of the brain is still downright rudimentary compared to our understanding of other organs. To revolutionize brain science, President Obama in April 2013 announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which is co-led by the National Science Foundation (NSF).

But even before BRAIN was created, NSF had a long history of funding innovative basic research focused on the brain. NSF's research approaches integrate information, methods and models at scales ranging from the molecular level to the behavioral level; they also draw from multiple scientific, engineering and computational disciplines.

In addition, some NSF-funded scientists are examining how changes in brain structure and activity correlate with different external environments and behavioral changes. These factors, along with genetic analyses, are--in many cases--easier to study in relatively simple organisms than in humans. Also, by identifying features that are similar and different across species, and by studying organisms throughout their lifespans, scientists are advancing their understanding of how nervous systems work.

Featured here are video interviews with selected NSF-funded brain researchers about their cutting-edge, multidisciplinary research on mice, octopuses, zebrafish, frogs, lizards and cichlids. These interviews were recorded at the NSF Workshop on Phylogenetic Principles of Brain Structure and Function at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Va., in October 2013.

Partha Mitra of Cold Spring Harbor Laboratory is currently focused on the Mouse Brain Architecture Project (MAP), which is aimed at creating 3-D maps of the mouse brain at various scales. (The mouse brain is 1/1000 of the volume of the human brain.) MAP is also dedicated to relating brain circuits (groups of neurons) to behavior.

One way that Mitra is contributing to MAP is by mapping the projection patterns of groups of similarly organized neurons across regions of the mouse brain. He is thereby helping to identify how neurons are connected and communicate across regions of the brain.

In addition, Mitra is applying his background in theoretical physics to his studies of the mouse brain. He is doing so by working to identify ways to apply to brain research methods in statistical physics that are used to analyze the macroscopic behavior of large, distributed networks.

Specifically, these methods have been used by engineers to analyze technologically important networks--such as power grids and coordinated formations of vehicles--and to help design such networks with wanted properties. If these methods can be applied to brain research, they may enable researchers to identify and prioritize important aspects of brain networks for study--helping to distinguish microscopic details that play important roles in overall behaviors from those that do not.

Once the map of the mouse brain is completed and analyzed, it will be the first-of-its-kind map of a whole vertebrate brain. MAP's future goals include mapping connectivity patterns in the marmoset monkey brain and ultimately in the human brain.

Information and images from MAP are publically available on MAP's website.

Clifton Ragsdale of the University of Chicago is researching the nervous system of the octopus, which is a successful predator partly because it has excellent eyesight--the best of any invertebrate. The octopus's excellent eyesight enables it to visually zero in and focus on prey.

What's more, each of the octopus's eight agile, boneless arms has about 44 million nerve cells (or almost 10 percent of all of its neurons). These arm neurons are connected to the animal's brain.

When an octopus spots a tasty-looking fish, the information it collects about this prey travels from the animal's eye to its brain. This information then travels through its arm neurons to help these soft-bodied contortionists determine how to snatch the prey.

Conversely, tactile information, such as the feel of a crab's rough shell, travels back through the octopus's arm neurons to its brain's learning and memory centers to help these clever animals improve their hunting skills.

Ragsdale is currently pioneering the use of modern molecular techniques to study how the octopus's unique nervous system processes visual information, and if its processing system significantly differs from those of vertebrates.

Melina Hale of the University of Chicago is studying neuronal circuits in zebrafish that generate startle responses. (Yes, the kinds of startle responses that are produced by sudden sounds or movements.)

Because little is known about how circuits operate in any organism and because startle responses are controlled by relatively simple circuits, an improved understanding of the circuitry of the zebrafish's startle responses is expected to help lay the groundwork for research on more complicated circuits.

The zebrafish--a small common aquarium fish--serves as an excellent fish for laboratory studies because molecular tools are available for experimenting with its neurons. The zebrafish can also be easily maintained and reproduces and develops rapidly. Also, young zebrafish are transparent and so their nervous systems are easily observable.

Walter Wilczynski of Georgia State University is researching how non-mammals signal one another in mating competitions, and how these signals influence the behavior of individual males and females. According to Wilczynski's research, an individual's behavioral responses to such signals and whether it loses or wins a mating competition may modify its brain in ways that may influence its future behavior.

Wilczynski's research is important because a) competition for reproduction is fundamental to all of biology; and b) Wilczynski uses model organisms whose social interactions are, in many ways, simplified versions of human social interactions. These model organisms include frogs, which communicate through vocal calls, and lizards, which communicate through visual displays.

Hans Hofmann of the University of Texas, Austin, is researching the influences of environment and genetics on the brains and behavior of cichlid fish. Cichlids provide excellent model organisms for such studies because thousands of species of cichlids have evolved; many of these species are genetically similar but behaviorally and socially different from one another. Hofmann is using the diversity of cichlid species to help identify which genes regulate various behaviors and evaluate how different social environments affect brain function and behavior.

Mammals and cichlids share many of the same genetic mechanisms that are sensitive to social environments and help govern mating systems (such as monogamous vs. non-monogamous systems) and parental care systems (such as those that involve fatherly caretaking vs. those that don't). Therefore, research on the effect of social environments on cichlid brains, genetics and behavior may ultimately help advance our understanding of differing human mating and parental care systems.

--  Lily Whiteman, NSF (703) 292-8310 lwhitema@nsf.gov
--  Sarah Bates, NSF (703) 292-7738 Sabates@nsf.gov

Investigators
Melina Hale
Hans Hofmann
Partha Mitra
Clifton Ragsdale
Walter Wilczynski

Related Institutions/Organizations
Harvard University
University of Chicago
Cold Spring Harbor Laboratory
Georgia State University Research Foundation, Inc.

Related Awards
#1344069 INSPIRE Track 1: Zero-One Laws at the Interface Between Physics, Engineering and Biology
#1021909 Octopus Neural Systems
#0818788 Integration of Ectopic Neurons into Motor Circuits
#0751573 The interaction of social experience and hormone changes in generating social status
#0217915 Collaborative Research: How Do Social and Habitat Complexities Shape Brain Structure?

Total Grants
$1,634,318

Related Websites
NSF fact sheet on BRAIN Initiative: http://www.nsf.gov/news/news_summ.jsp?cntn_id=128960
NSF article on BRAIN Initiative: http://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=128239

Partha Mitra
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Partha Mitra tells why and how he is helping to map the mouse brain.
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Clifton Ragsdale
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Clifton Ragsdale reveals why octopuses are such successful predators.
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Melina Hale
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Melina Hale explains how her research on zebrafish is helping to advance brain research.
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Walter Wilczynski
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Wilczynski discusses research on the responses by non-mammals to signals during mating competitions.
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Hans Hofmann
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Hofmann explains how environment and genetics influence the brains and behavior of cichlid fish.
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