BRAIN research is a focal point at Princeton

Thursday, Apr 18, 2013

On April 2 President Barack Obama announced the BRAIN initiative, a comprehensive research effort aimed at exploring how the brain works and providing new tools for understanding disorders such as Alzheimer's disease, schizophrenia, autism, epilepsy and traumatic brain injury. BRAIN stands for Brain Research through Advancing Innovative Neurotechnologies.

The Princeton Neuroscience Institute is home to numerous projects aimed at understanding the brain:

Virtual reality combined with cellular resolution population imaging

A critical goal of the BRAIN Initiative is to observe how circuits of brain cells process information in real time. David Tank, Princeton's Henry L. Hillman Professor in Molecular Biology and co-director of the Princeton Neuroscience Institute (PNI), leads a team that has created virtual reality systems in which laboratory mice can make choices to navigate through mazes and other environments while walking in place. This makes it possible to record from single neurons and populations of neurons in a functioning brain using advanced microscopic techniques that Tank helped pioneer. Princeton is a major center for the use of these methods, which are being used to study decision-making in the laboratory of Carlos Brody and sensory processing in the laboratory of Samuel Wang. Both are associate professors of molecular biology and PNI.

Development of new molecular sensors used in cellular imaging

Observation of brain circuits in action is possible with the help of fluorescent molecules engineered to change their brightness when a neuron is active. Wang is developing new sensors that respond more rapidly to cellular activity, as well as responding over a wider range of activity levels. These "molecular probes" are being tested and implemented in collaboration with Mala Murthy, assistant professor of molecular biology and PNI, and Lynn Enquist, department chair for molecular biology, member of PNI, and the Henry L. Hillman Professor in Molecular Biology.

Multiple electrode recording and methods for identifying neural signals

A major technology for recording circuit activity is the direct recording of electrical signals from many neurons at once. Michael Berry, associate professor of molecular biology and PNI, has conducted recordings covering the greatest number of neurons per unit area ever measured in the retina, a thin sheet of tissue at the back of the eye that encodes visual information to send to the brain. Berry also has developed superior algorithms for identifying the activity of these neurons. These algorithms are likely to find use by other researchers worldwide.

Brain circuitry and behavior

An essential question in understanding the brain is how does brain circuitry determine behavior? Ilana Witten, assistant professor of psychology and PNI, and Brody are addressing this question via a novel technique for controlling neuron activity using light. Known as optogenetics, the technique involves placing genetically encoded sensors that respond to light into neurons in the working brain. Applying light causes the brain cells to become active, opening up new ways to study the relationship between brain neural circuitry and behavior. Brody has also developed computerized training systems through which rodents can be trained to perform decision-making and memory tasks previously limited to study in higher species. Murthy has developed new quantitative methods to study behavior in flies, which have simple nervous systems, enabling researchers to establish links between neural circuit activity and behavior.

Tracing the connectivity in the nervous system

Neural activity is transmitted and coordinated through complex networks of connections that can appear hopelessly tangled. Enquist's laboratory uses viruses to trace these networks and pathways with exquisite specificity. Using viruses that hop across synaptic connections, Enquist and his collaborators can generate trails of fluorescent neurons that can be traced to reconstruct networks that join distant brain regions with one another. Sabine Kastner, professor of psychology and PNI, is developing methods to first map connection pathways between areas in the brain using a form of magnetic resonance imaging and then target neural recording to the connected regions to study how behavioral state affects the synchronization of activity.

Tracing these neurons is an essential component of creating a map of brain activity. The brain can be thought of as an assemblage of hundreds of brain regions that talk with one another over long distances. Tools such as Enquist's viruses and Kastner's MRI methods will help reveal these channels of communication.

Theoretical and analytical tools for understanding the brain

Brain imaging and recording methods produce enormous quantities of data. One of the most important technical innovations is the development of new ways of examining and analyzing this data. A major focus is understanding how information relevant to behavior is represented in the patterns of neural activity, a problem known as neural coding. PNI researchers William Bialek, Princeton's John Archibald Wheeler/Battelle Professor in Physics and the Lewis-Sigler Institute for Integrative Genomics, as well as Berry, Brody and Tank have developed approaches for characterizing neural codes in multi-neuron recordings.

The approaches explored at Princeton also extend to human brain imaging using functional magnetic resonance imaging (fMRI). David Blei, associate professor of computer science, and Kenneth Norman, associate professor of psychology and PNI, are working to develop better algorithms to decode cognitive state information from human brain imaging data. Neural decoding techniques developed at Princeton are being used by dozens of labs worldwide. Algorithms for characterizing the correlations of activity among different brain regions are under development by Jonathan Cohen, co-director of PNI and the Robert Bendheim and Lynn Bendheim Thoman Professor in Neuroscience; Nicholas Turk-Browne, assistant professor of psychology; and Kai Li, the Paul M. Wythes '55 P86 and Marcia R. Wythes P86 Professor in Computer Science.

The Princeton Neuroscience Institute is home to three centers of research:

  • The recently established Bezos Center for Neural Circuit Dynamics is enabling researchers to develop techniques and instrumentation that contribute directly to mapping neural activity in the functioning brain using optical tools and multi-electrode recording. These are being combined with optogenetics, which involves using light to manipulate brain cells, and connectomics, the study of connections between neurons.
  • The Scully Center for the Neuroscience of Mind and Behavior supports the convergence of neuroscience and psychology to better understand the brain's role in behavior and is home to human brain imaging facilities.
  • The McDonnell Center for Systems Neuroscience supports teaching in the institute as well as providing funding for instrumentation and facilities useful at all levels of brain organization.