Marcelo O. Magnasco - US grants

DESCRIPTION (provided by applicant): This project is a collaboration using computational, theoretical, and experimental approaches to analyze early events in hearing, at various scales ranging from the motion of hair bundles to neural coding in the auditory nerve. The recent focus of the collaboration has been the active process that injects mechanical energy into the cochlea to assist the mechanical amplification of signals, in particular the hypothesis that the active process poises the organ's elements at the threshold of an oscillatory instability, called a Hopf bifurcation. The current focus extends to examine the interaction of the active process with its environment: adaptive mechanisms, other elements, and downstream processing. At the microscopic scale the environment of the active process consists of the adaptation mechanisms that regulate it and keep it poised, and detailed analysis of various candidate mechanisms is proposed. At the mesoscopic scale the environment includes other nearby active elements: the focus will be the interactions between hair cells in the whole cochlea, and the mechanism and process through which the dynamical behavior of each hair cell contributes to the overall function of the cochlea without a massive cacophony of feedback oscillations. The outcome would be a theory of what the observed responses should be, given the microscopic model. At the coarsest level the encoding of the auditory stream into the acoustic nerve will be studied, particularly how level-independent auditory percepts can be extracted from the level-dependent responses of the cochlea. Elucidation of the dynamical principles of cochlea behavior would likely guide newer generations of cochlear implants, aid in the design of pharmacological intervention, and help understand whether the ear's amplifies can be protected or recovered from damage. Similarly, elucidation of the principles of auditory neural coding should provide deeper guiding principles for voice recognition and other technology to assist the hearing impaired.

The vertebrate nervous system consists of neurons that interact with each other through connections, called synapses. Changes in the strengths of the synaptic connections, due to the activity patterns of the neurons, are thought to underlie the plasticity of the brain. Furthermore, it is widely recognized that a delicate balancing of synaptic connection strength is essential to nervous system function. Unhindered connections would cause the brain to cease to operate, in a cacophony of epileptic-like feedback oscillations; if suppression dominated, stimuli would be unable to elicit a response from an apathetic, flatline brain. At the delicate interface between these two useless modes of behavior lies a regime in which groups of neurons are on the verge of oscillation, and may rapidly start or stop responding according to external influences.
This project will develop a theory of self-poising, in which local activity-dependent rules for balancing synaptic response result in many groups of neurons poised at the edge of this dynamical instability. The theory will develop the interaction between self-poising and microstructure, in which local neuronal microcircuits are threaded together into global states, and the interaction with macrostructure, in which different self-poised areas communicate and interact.
New theory resulting from this project will aid understanding of global activity patterns in the brain, such as Electroencephalography (EEG) or Electrocorticography (ECoG). The proposed research will contribute directly to education and outreach programs for high school students, undergraduate and graduate students, and postdoctoral researchers. These activities will be coordinated through ongoing programs at Rockefeller University. Promoting the involvement of minority undergraduate and graduate students in research environments will be a priority of this program. Results from the project will be incorporated into novel graduate courses on network theory and advanced modeling for biology students.

It has been known since the time of Edison that optimally distributing fungible goods, such as electricity or water, requires hierarchical systems consisting of trunks, mains and subsidiaries. Most biological distribution networks are hierarchical in this sense, and their elements come in vastly different sizes. But also, many biological distribution networks, such as the veins of a leaf, the arterioles in the surface of the cerebral cortex, or the veins of a dragonfly wing, have a fabric-like texture. Such networks do not only contain the links with the most direct route from the source, but also many cross-bracing connections, that permit it to continue functioning even when elements are damaged or temporarily clogged, and to maximize capacity when only part of the organism is demanding the good. The cross-bracing connections form closed loops, and they themselves are hierarchical, so the networks look like little loops nested within larger loops, not unlike networks of highways, avenues, streets and alleys.

This project will develop the theory of such loopy hierarchical architectures, with a particular emphasis to understanding how the tradeoffs between the different and often conflicting requirements of minimal cost, resistance to damage, resistance to fluctuating loads, and maximum acceptable gradients result in the complex, beautiful and subtly distinct patterns observed in nature. The PI will develop mathematical ways, given a natural exemplar of such patterns, to read off from its the architecture the particular combination of costs that shaped it. These methods will be applied to a large database of leaves, to try to correlate their architectural differences with their environment and physiology. Finally, artificial versions of these networks will be generated and their performance characterized experimentally. New theory and experimental data from this project will illuminate our understanding, not only of the plant kingdom, but also of design principles for our own vascular systems.

The proposed research will contribute directly to education and outreach programs for high school students, undergraduate and graduate students, and postdoctoral researchers. These activities will be coordinated through ongoing programs at Rockefeller University. Promoting the involvement of minority undergraduate and graduate students in research environments will be a priority of this program. Results from the project will be incorporated into novel graduate courses on network theory and advanced modeling for biology students.

This project was developed during a NSF Ideas Lab on "Cracking the Olfactory Code" and is jointly funded by the Chemistry of Life Processes program in the Chemistry Division, the Mathematical Biology program in the Division of Mathematical Sciences, the Physics of Living Systems program in the Physics Division, the Neural Systems Cluster in the Division of Integrative Organismal Systems, the Division of Biological Infrastructure, and the Division of Emerging Frontiers.

The mammalian sense of smell is arguably the most complex sensory system in the animal kingdom. Hundreds of olfactory receptors are deployed to detect a vast array of chemicals with exquisite sensitivity in complex environments. This collaborative project combines biochemistry, neurobiology, genomics, mathematics and new technologies to understand how the mammalian olfactory system detects, encodes and extracts meaning from chemical stimuli. The goals of this project are to: (1) elucidate fundamental neural mechanisms for how chemical sensation turns into the perception of a smell; (2) produce a vast array of scientific resources to olfactory scientists; (3) provide valuable information for broader audiences, including for molecular evolution, chemical ecology, and flavor and fragrance communities; (4) establish new technologies and mathematical frameworks to study biological systems; and (5) facilitate applied chemical sensing technologies for environmental monitoring, food safety, and homeland security. The project also offers training opportunities from the high school to the postdoctoral trainee level, and educational opportunities and outreach through partnerships with local science museums as well as science learning centers and their media outlets.

This project's efforts are organized around three aims that focus on how information about odor identity and odor valence (attractiveness/aversiveness) is encoded at the level of olfactory receptors (Aim 1); within the olfactory bulb, where odor information is first processed (Aim 2); and the cortical amygdala, where odor codes may integrate with other information streams (Aim 3). Completion of the project entails the development and use a broad array of innovative approaches that include mapping all human and mouse odorant receptors to the chemicals they bind, defining the innate valence of these chemicals using behavioral assays, mapping all odorant receptor projections to the olfactory bulb, functionally characterizing their neural representations in the olfactory bulb and cortical amygdala, and using novel mathematical approaches to understand the underlying structure of odor coding and olfactory neural circuits at the level of sensory neurons, olfactory bulb glomeruli, and amygdala. Progress towards each aim involves close collaborations between team members with diverse expertise, including molecular biology, behavioral neuroscience, in vivo functional imaging, and mathematical and theoretical analysis of complex datasets. The multidisciplinary strategy implemented here promises to lead to an integrated and comprehensive understanding of how mammals sense and make sense of their chemical environments.

This project will address central questions in dolphin communication research by aggressively attacking the key technical issues such as the attribution problem with state-of-the-art computational neuroscience and statistical physics methods. The project will move quantitative high-throughput studies, currently tied to the bench, into field research of wild animals. This interdisciplinary study is collaboration between the labs of animal cognitive psychologist Diana Reiss and physicist and computational neuroscientist Marcelo Magnasco. One of the broader impacts of the project, the aquarium studies are particularly conducive to outreach efforts since the dolphin related activities take place in an open amphitheater environment and the exhibit has changed from dolphin shows to more educational demonstrations about animal care, behavior, and conservation. The research activities will take place concurrently with visits of the public and field trips of schoolchildren and therefore, the research endeavor is being communicated to the public in real time. Virtually all the activities proposed can, with modest effort and cost, be made into an open exhibit at the National Aquarium in Baltimore, instructing visiting schoolchildren on the research process and on collaborative research across scientific boundaries. The field trips to the research sites are organized jointly with undergraduate and graduate courses in field research for Hunter College students and are excellent opportunities to showcase and engage actual cutting edge research to these students.

The cognitive and communication capabilities of dolphins are legendary. Untangling the legends into a body of rigorous science has been a slow process fraught with many pitfalls; rigorous work in the last two decades has painted a rather more nuanced picture than the legends. While dolphins do indeed have amazing cognitive abilities, their natural conspecific communication in the wild remains enigmatic, with ongoing debates as to the nature of many elements of their vocal repertoire and the complexity of their communication overall. The key technical problems have been the laboriousness of the attribution problem, the assignment of which animal emitted which vocalization, the lack of automated behavior analysis methods, and finally the linking of attributed vocalizations to specific behaviors. Because we currently cannot automatically triangulate and track their voices underwater there are no extant corpora of dolphin vocalizations: what have been studied are mostly isolated calls, as opposed to "conversations". In the last decade, studies in songbirds and rodents have demonstrated the power of high-throughput setups in which a large number of animals are studied through automated means. The overarching aim of this project is to extend these high-throughput settings to dolphin communication studies, in captivity and in the wild, and develop, for this far more difficult case, the relevant automated audio and video analysis tools to handle the huge amount of data generated. There are two specific activities: first, the PIs will study learning and free use of a synthetic language and second record from multiple vantage points and then computationally analyze natural dolphin behavior in the wild, both during natural behavior in pods as well as during highly circumscribed, specific behaviors such as bowriding. The corpora of vocalizations generated will be analyzed computationally to establish whether wild dolphins do have a rich-enough "language", as opposed to a repertoire of calls.

The cognitive and communication prowess of the large-brained, highly gregarious bottlenose dolphin is legendary and has captured the interest and imagination of scientists and the public at large. Notably, dolphins are one of a handful of species that are vocal learners; thus the dolphin presents us with a unique and alternative model to songbirds to advance our understanding of the processes that underlie vocal learning and communication in a large-brained mammal showing high social and behavioral complexity. Despite decades of research on dolphin vocal communication, the constituent elements, the sequential and temporal organization of the elements, and the nature of vocal transactions between dolphins remain enigmatic. In order to decipher dolphin communication and further elucidate these issues, the PIs will use observational approaches in the wild and in an aquarium as well as two experimental approaches in an aquarium. A first approach studies how dolphins coordinate their behavior in the face of novelty: How do dolphins synchronize their behavior when requested to present novel behaviors in tandem? How do they succeed in working as a team when confronted with a new challenge? In a second approach, the researchers will provide dolphins with a two-way, interactive touchscreen and audio system. Their proclivity for vocal learning and their other cognitive processes will be probed by giving them choice and control over the interactive system and observing and documenting how they use and respond to the contingencies of their interactions, which shall be obtaining novel acoustic signals temporally paired with objects, interactions or activities. The aquarium studies are particularly conducive to outreach efforts and informal science education since the dolphin-related activities will be conducted in an open amphitheater environment at a leading aquarium. The exhibit has changed from dolphin shows to more educational demonstrations about animal care, behavior, and conservation. The research activities will take place concurrently with visits of the public and field trips of school children and therefore, the research endeavor will be communicated to the public in real time. Virtually all the activities proposed can, with modest effort and cost, be made into an open exhibit at the National Aquarium in Baltimore, instructing visiting schoolchildren on the research process and on collaborative research across scientific boundaries. The field trips to the research sites are organized jointly with undergraduate and graduate courses in field research for Hunter College students and are excellent opportunities to showcase and engage actual cutting edge research to these students. This tightly-knit interdisciplinary collaboration between the labs of animal cognitive psychologist and marine mammal scientist and physicist, computational neuroscientist and bio-acoustician, seeks to and extend high-throughput settings to dolphin communication studies in captivity.

A key intellectual merit of this proposal is to address these fundamental questions in the field of animal cognition and communication through powerful methods drawn from statistical mechanics, machine learning, and signal processing. Central technical problems in "decoding" dolphin communication are the difficulty in sound localization and attributing the detected vocalizations to specific individual dolphins, the lack of automated behavioral analysis methods, and the crucial step of creating an integrated picture of attributed vocal and behavioral transactions or "conversations" that can be subjected to high-through analysis. Another technical problem is the design and deployment of an advanced two-way interactive system consisting of an underwater touchpad and real-time audio input/output, plus the associated set of interaction interfaces. Finally, this project also addresses important technical problems in the deployment of aerial and aquatic drones for field studies.

This award will support the participation of researchers working on the Physics of Living Systems (PoLS) at the 27th International Conference on Statistical Physics, StatPhys27, which will be held in Buenos Aires, Argentina in July 2019. It is expected that StatPhys27 will bring together about 700 participants from all over the world, including senior and young researchers and graduate students. Statistical Physics is largely interdisciplinary, so that the participation of researchers with diverse scientific backgrounds is expected. StatPhys27 will last for five days. Associated to StatPhys27 there will be an outreach activity with three talks for the general public at the National Science Museum. Two of the talks will be in the field of PoLS. There will also be sessions on human rights and on inclusion and diversity in physics and an outreach activity for the general public. Taking active part in StatPhys27 will allow the researchers working in the field of PoLS to reach out to new communities of students and researchers. The plenary talks of StatPhys27 will be videotaped and made available at the conference website. The possibility of streaming them live over the Internet is under consideration. The International Centre for Theoretical Physics of Trieste (ICTP) has offered to set up a special conference room at its premises where people could watch the video-streaming. Thus, StatPhys27 is expected to have a huge impact in various places. Furthermore, the outreach activity that is planned to take place at the Science Museum in Buenos Aires will allow the general public to learn about the subjects of statistical physics and the physics of living systems.

StatPhys is the largest and most prestigious conference on the nowadays broadly interdisciplinary area of statistical physics. Held triennially in different parts of the world, it attracts most of the community that does research on the subject. Ten renowned scientists will give plenary talks and another 30 will do so at one of the four planned parallel sessions of StatPhys27. The conference will also host the Boltzmann Medal and Young Scientist in Statistical Physics ceremonies. The recipient of the prestigious Boltzmann Medal will give a plenary talk. StatPhys27 will embrace a variety of subjects including Physics of Living Systems, Complex and Interdisciplinary Systems, Soft Matter, Out-of-equilibrium phenomena and Nonlinear Physics, etc.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.